Editing Cell nucleus

{{short description|Eukaryotic membrane-bounded organelle containing DNA}}
{{pp-vandalism|expiry=indef|small=yes}}
{{Use dmy dates|date=August 2018}}
[[File:HeLa cells stained with Hoechst 33258.jpg|thumb|upright=1.35|right|[[HeLa|HeLa cells]] stained for [[nuclear DNA]] with the blue [[fluorescent]] [[Hoechst stain|Hoechst dye]]. The central and rightmost cells are in [[interphase]], thus their entire nuclei are labeled. On the left, a cell is going through [[mitosis]] and its DNA has condensed.]]
{{Organelle diagram}}

The '''cell nucleus''' ({{etymology|la|{{wikt-lang|la|nucleus}} or {{wikt-lang|la|nuculeus}}|kernel, seed}}; {{plural form}}: '''nuclei''') is a [[membrane-bound organelle]] found in [[eukaryote|eukaryotic]] [[cell (biology)|cells]]. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian [[red blood cell]]s, have [[#Anucleated_cells|no nuclei]], and a few others including [[osteoclast]]s have [[Multinucleate|many]]. The main structures making up the nucleus are the [[nuclear envelope]], a double membrane that encloses the entire organelle and isolates its contents from the cellular [[cytoplasm]]; and the [[nuclear matrix]], a network within the nucleus that adds mechanical support.

The cell nucleus contains nearly all of the cell's [[genome]]. [[Nuclear DNA]] is often organized into multiple [[chromosome]]s – long strands of [[DNA]] dotted with various [[protein]]s, such as [[histone]]s, that protect and organize the DNA. The [[gene]]s within these chromosomes are [[Nuclear organization|structured]] in such a way to promote cell function. The nucleus maintains the integrity of genes and controls the activities of the cell by regulating [[gene expression]].

Because the nuclear envelope is impermeable to [[Macromolecule|large molecules]], [[nuclear pore]]s are required to regulate [[nuclear transport]] of molecules across the envelope. The pores cross both nuclear membranes, providing a [[Ion channel|channel]] through which larger molecules must be [[Active transport|actively transported]] by carrier proteins while allowing free movement of small molecules and [[ion]]s. Movement of large molecules such as proteins and [[RNA]] through the pores is required for both gene expression and the maintenance of chromosomes. Although the interior of the nucleus does not contain any membrane-bound subcompartments, a number of [[nuclear bodies]] exist, made up of unique proteins, RNA molecules, and particular parts of the chromosomes. The best-known of these is the [[nucleolus]], involved in the assembly of [[ribosome]]s.

==Chromosomes==
{{Main|Chromosome}}
{{Further|Nuclear organization}}

[[Image:MouseChromosomeTerritoriesBMC Cell Biol6-44Fig2e.jpg|thumb|200px|A mouse [[fibroblast]] nucleus in which [[DNA]] is stained blue. The distinct chromosome territories of chromosome 2 (red) and chromosome 9 (green) are stained with [[fluorescent in situ hybridization]].]]

The cell nucleus contains the majority of the cell's genetic material in the form of multiple linear DNA molecules organized into structures called [[chromosome]]s. Each human cell contains roughly two meters of DNA.<ref name = "Lodish" />{{rp|405}} During most of the [[cell cycle]] these are organized in a DNA-protein complex known as [[chromatin]], and during cell division the chromatin can be seen to form the well-defined chromosomes familiar from a [[karyotype]]. A small fraction of the cell's genes are located instead in the [[mitochondria]].<ref name = "Lodish" />{{rp|438}}

There are two types of chromatin. [[Euchromatin]] is the less compact DNA form, and contains genes that are frequently [[gene expression|expressed]] by the cell.<ref name="Ehrenhofer">{{cite journal | vauthors = Ehrenhofer-Murray AE | title = Chromatin dynamics at DNA replication, transcription and repair | journal = European Journal of Biochemistry | volume = 271 | issue = 12 | pages = 2335–49 | date = June 2004 | pmid = 15182349 | doi = 10.1111/j.1432-1033.2004.04162.x | department = Review | doi-access = free }}</ref> The other type, [[heterochromatin]], is the more compact form, and contains DNA that is infrequently transcribed. This structure is further categorized into [[Facultative heterochromatin#Facultative heterochromatin|''facultative'' heterochromatin]], consisting of genes that are organized as heterochromatin only in certain cell types or at certain stages of development, and [[Constitutive heterochromatin|''constitutive'' heterochromatin]] that consists of chromosome structural components such as [[telomere]]s and [[centromere]]s.<ref name="Grigoryev">{{cite journal | vauthors = Grigoryev SA, Bulynko YA, Popova EY | title = The end adjusts the means: heterochromatin remodelling during terminal cell differentiation | journal = Chromosome Research | volume = 14 | issue = 1 | pages = 53–69 | year = 2006 | pmid = 16506096 | doi = 10.1007/s10577-005-1021-6 | s2cid = 6040822 | department = Review }}</ref> During interphase the chromatin organizes itself into discrete individual patches,<ref name="Schardin">{{cite journal | vauthors = Schardin M, Cremer T, Hager HD, Lang M | title = Specific staining of human chromosomes in Chinese hamster x man hybrid cell lines demonstrates interphase chromosome territories | journal = Human Genetics | volume = 71 | issue = 4 | pages = 281–7 | date = December 1985 | pmid = 2416668 | doi = 10.1007/BF00388452 | url = https://epub.ub.uni-muenchen.de/9272/1/cremer_thomas_9272.pdf | s2cid = 9261461 | department = Primary }}</ref> called ''[[chromosome territories]]''.<ref name="Lamond">{{cite journal | vauthors = Lamond AI, Earnshaw WC | title = Structure and function in the nucleus | journal = Science | volume = 280 | issue = 5363 | pages = 547–53 | date = April 1998 | pmid = 9554838 | doi = 10.1126/science.280.5363.547 | url = http://azolla.fc.ul.pt/aulas/BiologiaCelular/docs/nucleo.pdf | citeseerx = 10.1.1.323.5543 | department = Review }}</ref> Active genes, which are generally found in the euchromatic region of the chromosome, tend to be located towards the chromosome's territory boundary.<ref name="Kurz">{{cite journal | vauthors = Kurz A, Lampel S, Nickolenko JE, Bradl J, Benner A, Zirbel RM, Cremer T, Lichter P | display-authors = 6 | title = Active and inactive genes localize preferentially in the periphery of chromosome territories | journal = The Journal of Cell Biology | volume = 135 | issue = 5 | pages = 1195–205 | date = December 1996 | pmid = 8947544 | pmc = 2121085 | doi = 10.1083/jcb.135.5.1195 | url = http://intl.jcb.org/cgi/content/abstract/135/5/1195 | url-status = dead | department = Primary | archive-url = https://web.archive.org/web/20070929104104/http://intl.jcb.org/cgi/content/abstract/135/5/1195 | archive-date = 29 September 2007 }}</ref>

Antibodies to certain types of chromatin organization, in particular, [[nucleosome]]s, have been associated with a number of [[autoimmune disease]]s, such as [[systemic lupus erythematosus]].<ref name="Rothfield">{{cite journal | vauthors = Rothfield NF, Stollar BD | title = The relation of immunoglobulin class, pattern of anti-nuclear antibody, and complement-fixing antibodies to DNA in sera from patients with systemic lupus erythematosus | journal = The Journal of Clinical Investigation | volume = 46 | issue = 11 | pages = 1785–94 | date = November 1967 | pmid = 4168731 | pmc = 292929 | doi = 10.1172/JCI105669 | department = Primary }}</ref> These are known as [[anti-nuclear antibody|anti-nuclear antibodies]] (ANA) and have also been observed in concert with [[multiple sclerosis]] as part of general immune system dysfunction.<ref name="Barned">{{cite journal | vauthors = Barned S, Goodman AD, Mattson DH | title = Frequency of anti-nuclear antibodies in multiple sclerosis | journal = Neurology | volume = 45 | issue = 2 | pages = 384–5 | date = February 1995 | pmid = 7854544 | doi = 10.1212/WNL.45.2.384 | s2cid = 30482028 | department = Primary }}</ref>

==Nuclear structures and landmarks==
{{Further|Nuclear equivalence}}
[[Image:Diagram human cell nucleus.svg|thumb|280px|right|Diagram of the nucleus showing the [[ribosome]]-studded [[outer nuclear membrane]], [[nuclear pores]], [[DNA]] (complexed as [[chromatin]]), and the [[nucleolus]].]]

The nucleus contains nearly all of the cell's [[DNA]], surrounded by a network of fibrous [[intermediate filaments]] called the [[nuclear matrix]], and is  enveloped in a double membrane called the [[nuclear envelope]]. The nuclear envelope separates the fluid inside the nucleus, called the [[nucleoplasm]], from the rest of the cell. The size of the nucleus is correlated to the size of the cell, and this [[NC ratio|ratio]] is reported across a range of cell types and species.<ref name="Kume">{{cite journal |vauthors=Kume K, Cantwell H, Neumann FR, Jones AW, Snijders AP, Nurse P |title=A systematic genomic screen implicates nucleocytoplasmic transport and membrane growth in nuclear size control |journal=PLOS Genet |volume=13 |issue=5 |pages=e1006767 |date=May 2017 |pmid=28545058 |pmc=5436639 |doi=10.1371/journal.pgen.1006767 |url= |doi-access=free }}</ref> In eukaryotes the nucleus in many cells typically occupies 10% of the cell volume.<ref name=Alberts2015/>{{rp|178}} The nucleus is the largest [[organelle]] in animal cells.<ref name="Lodish_2016"/>{{rp|12}} In human cells, the diameter of the nucleus is approximately six  [[micrometre]]s (μm).<ref name=Alberts2015/>{{rp|179}}

===Nuclear envelope and pores===
{{Main|Nuclear envelope|Nuclear pore}}

[[Image:NuclearPore crop.svg|thumb|right|250px|A cross section of a [[nuclear pore]] on the surface of the [[nuclear envelope]] (1). Other diagram labels show (2) the outer ring, (3) spokes, (4) basket, and (5) filaments.]]

The [[nuclear envelope]] consists of two [[cell membrane|membranes]], an [[Inner nuclear membrane|inner]] and an [[outer nuclear membrane]], perforated by [[nuclear pore]]s.<ref name=Alberts2015>{{cite book|title=Molecular Biology of the Cell |edition=6 |vauthors=Alberts B, Johnson A, Lewis J, Morgan D, Raff M, Roberts K, Walter P |publisher=Garland Science |date=2015 |location=New York}}</ref>{{rp|649}} Together, these membranes serve to separate the cell's genetic material from the rest of the cell contents, and allow the nucleus to maintain an environment distinct from the rest of the cell. Despite their close apposition around much of the nucleus, the two membranes differ substantially in shape and contents. The inner membrane surrounds the nuclear content, providing its defining edge.<ref name="Lodish_2016"/>{{rp|14}} Embedded within the inner membrane, various proteins bind the intermediate filaments that give the nucleus its structure.<ref name=Alberts2015/>{{rp|649}} The outer membrane encloses the inner membrane, and is continuous with the adjacent [[endoplasmic reticulum]] membrane.<ref name=Alberts2015/>{{rp|649}} As part of the endoplasmic reticulum membrane, the outer nuclear membrane is studded with [[ribosome]]s that are actively translating proteins across membrane.<ref name=Alberts2015/>{{rp|649}} The space between the two membranes is called the perinuclear space, and is continuous with the endoplasmic reticulum [[Lumen (anatomy)|lumen]].<ref name=Alberts2015/>{{rp|649}}

In a mammalian nuclear envelope there are between 3000 and 4000 [[nuclear pore complex]]es (NPCs) perforating the envelope.<ref name=Alberts2015/>{{rp|650}} Each NPC contains an eightfold-symmetric ring-shaped structure at a position where the inner and outer membranes fuse.<ref name="Shulga">{{cite journal | vauthors = Shulga N, Mosammaparast N, Wozniak R, Goldfarb DS | title = Yeast nucleoporins involved in passive nuclear envelope permeability | journal = The Journal of Cell Biology | volume = 149 | issue = 5 | pages = 1027–38 | date = May 2000 | pmid = 10831607 | pmc = 2174828 | doi = 10.1083/jcb.149.5.1027 | department = Primary }}</ref> The number of NPCs can vary considerably across cell types; small [[glial cell]]s only have about a few hundred, with large [[Purkinje cell]]s having around 20,000.<ref name=Alberts2015/>{{rp|650}} The NPC provides selective transport of molecules between the [[nucleoplasm]] and the [[cytosol]].<ref name="Alberts2019">{{cite book |last1=Alberts |first1=Bruce |title=Essential cell biology |date=2019 |location=New York |isbn=9780393680393 |page=242 |edition=Fifth}}</ref> The nuclear pore complex is composed of approximately thirty different proteins known as [[nucleoporin]]s.<ref name=Alberts2015/>{{rp|649}} The pores are about 60–80 million [[atomic mass unit|daltons]] in [[molecular weight]] and consist of around 50 (in [[yeast]]) to several hundred proteins (in [[vertebrate]]s).<ref name = "Lodish_2016">{{cite book | vauthors = Lodish HF, Berk A, Kaiser C, Krieger M, Bretscher A, Ploegh H, Amon A, Martin KC, Darnell JE | display-authors = 6 | title = Molecular Cell Biology | date = 2016 | publisher = W.H. Freeman | location = New York | isbn = 978-1-4641-8339-3 | edition = Eighth }}</ref>{{rp|622–4}} The pores are 100&nbsp;nm in total diameter; however, the gap through which molecules freely diffuse is only about 9&nbsp;nm wide, due to the presence of regulatory systems within the center of the pore. This size selectively allows the passage of small water-soluble molecules while preventing larger molecules, such as [[nucleic acid]]s and larger proteins, from inappropriately entering or exiting the nucleus. These large molecules must be actively transported into the nucleus instead. Attached to the ring is a structure called the '''nuclear basket''' that extends into the nucleoplasm, and a series of filamentous extensions that reach into the cytoplasm. Both structures serve to mediate binding to nuclear transport proteins.<ref name="Lodish">{{cite book | vauthors = Lodish H, Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipursky SL, Darnell J | title = Molecular Cell Biology | publisher = WH Freeman | edition = 5th | year = 2004 | location = New York | isbn = 978-0-7167-2672-2 | url-access = registration | url = https://archive.org/details/studentcompanion0000unse_r7k2 }}</ref>{{rp|509–10}}

Most proteins, ribosomal subunits, and some RNAs are transported through the pore complexes in a process mediated by a family of transport factors known as [[karyopherin]]s. Those karyopherins that mediate movement into the nucleus are also called importins, whereas those that mediate movement out of the nucleus are called exportins. Most karyopherins interact directly with their cargo, although some use [[Signal transducing adaptor protein|adaptor proteins]].<ref name="Pemberton">{{cite journal | vauthors = Pemberton LF, Paschal BM | title = Mechanisms of receptor-mediated nuclear import and nuclear export | journal = Traffic | volume = 6 | issue = 3 | pages = 187–98 | date = March 2005 | pmid = 15702987 | doi = 10.1111/j.1600-0854.2005.00270.x | s2cid = 172279 | department = Review | doi-access = free }}</ref> [[Steroid hormone]]s such as [[cortisol]] and [[aldosterone]], as well as other small lipid-soluble molecules involved in intercellular [[cell signaling|signaling]], can diffuse through the cell membrane and into the cytoplasm, where they bind [[nuclear receptor]] proteins that are trafficked into the nucleus. There they serve as [[transcription factor]]s when bound to their [[Ligand (biochemistry)|ligand]]; in the absence of a ligand, many such receptors function as [[histone deacetylase]]s that repress gene expression.<ref name="Lodish"/>{{rp|488}}

===Nuclear lamina===
{{Main|Nuclear lamina}}
In animal cells, two networks of [[intermediate filaments]] provide the nucleus with mechanical support: The [[nuclear lamina]] forms an organized meshwork on the internal face of the envelope, while less organized support is provided on the cytosolic face of the envelope. Both systems provide structural support for the nuclear envelope and anchoring sites for chromosomes and nuclear pores.<ref name="MBoC">{{cite book | year = 2002 | title = Molecular Biology of the Cell | chapter = Chapter 4: DNA and Chromosomes | pages = 191–234 | veditors = Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P | location = New York | publisher = Garland Science | edition = 4th | isbn = 978-0-8153-4072-0 }}</ref>

The nuclear lamina is composed mostly of [[lamin]] proteins. Like all proteins, lamins are synthesized in the cytoplasm and later transported to the nucleus interior, where they are assembled before being incorporated into the existing network of nuclear lamina.<ref name="Sturrman">{{cite journal | vauthors = Stuurman N, Heins S, Aebi U | title = Nuclear lamins: their structure, assembly, and interactions | journal = Journal of Structural Biology | volume = 122 | issue = 1–2 | pages = 42–66 | year = 1998 | pmid = 9724605 | doi = 10.1006/jsbi.1998.3987 | department = Review }}</ref><ref name="Goldman">{{cite journal | vauthors = Goldman AE, Moir RD, Montag-Lowy M, Stewart M, Goldman RD | title = Pathway of incorporation of microinjected lamin A into the nuclear envelope | journal = The Journal of Cell Biology | volume = 119 | issue = 4 | pages = 725–35 | date = November 1992 | pmid = 1429833 | pmc = 2289687 | doi = 10.1083/jcb.119.4.725 | department = Primary }}</ref> Lamins found on the cytosolic face of the membrane, such as [[emerin]] and [[nesprin]], bind to the cytoskeleton to provide structural support. Lamins are also found inside the nucleoplasm where they form another regular structure, known as the ''nucleoplasmic veil'',<ref name="RGoldman">{{cite journal | vauthors = Goldman RD, Gruenbaum Y, Moir RD, Shumaker DK, Spann TP | title = Nuclear lamins: building blocks of nuclear architecture | journal = Genes & Development | volume = 16 | issue = 5 | pages = 533–47 | date = March 2002 | pmid = 11877373 | doi = 10.1101/gad.960502 | doi-access = free | department = Review }}</ref><ref name="Broers_2004">{{cite journal | vauthors = Broers JL, Ramaekers FC | title = Dynamics of nuclear lamina assembly and disassembly | journal = Symposia of the Society for Experimental Biology | issue = 56 | pages = 177–92 | date = 2004 | pmid = 15565881 | isbn = 9781134279838 | url = https://books.google.com/books?id=lpR5AgAAQBAJ&pg=PA189 | department = Review }}</ref> that is visible using [[fluorescence microscopy]]. The actual function of the veil is not clear, although it is excluded from the nucleolus and is present during [[interphase]].<ref name="Moir">{{cite journal | vauthors = Moir RD, Yoon M, Khuon S, Goldman RD | title = Nuclear lamins A and B1: different pathways of assembly during nuclear envelope formation in living cells | journal = The Journal of Cell Biology | volume = 151 | issue = 6 | pages = 1155–68 | date = December 2000 | pmid = 11121432 | pmc = 2190592 | doi = 10.1083/jcb.151.6.1155 | department = Primary }}</ref> Lamin structures that make up the veil, such as [[LEM domain-containing protein 3|LEM3]], bind chromatin and disrupting their structure inhibits transcription of protein-coding genes.<ref name="Spann">{{cite journal | vauthors = Spann TP, Goldman AE, Wang C, Huang S, Goldman RD | title = Alteration of nuclear lamin organization inhibits RNA polymerase II-dependent transcription | journal = The Journal of Cell Biology | volume = 156 | issue = 4 | pages = 603–8 | date = February 2002 | pmid = 11854306 | pmc = 2174089 | doi = 10.1083/jcb.200112047 | department = Primary }}</ref>

Like the components of other intermediate filaments, the lamin [[monomer]] contains an [[alpha-helix|alpha-helical]] domain used by two monomers to coil around each other, forming a [[protein dimer|dimer]] structure called a [[coiled coil]]. Two of these dimer structures then join side by side, in an [[Antiparallel (biochemistry)|antiparallel]] arrangement, to form a [[tetramer protein|tetramer]] called a ''protofilament''. Eight of these protofilaments form a lateral arrangement that is twisted to form a ropelike ''filament''. These filaments can be assembled or disassembled in a dynamic manner, meaning that changes in the length of the filament depend on the competing rates of filament addition and removal.<ref name="MBoC" />

Mutations in lamin genes leading to defects in filament assembly cause a group of rare genetic disorders known as ''[[laminopathies]]''. The most notable laminopathy is the family of diseases known as [[progeria]], which causes the appearance of premature [[aging]] in those with the condition. The exact mechanism by which the associated [[biochemistry|biochemical]] changes give rise to the aged [[phenotype]] is not well understood.<ref name="Mounkes">{{cite journal | vauthors = Mounkes LC, Stewart CL | title = Aging and nuclear organization: lamins and progeria | journal = Current Opinion in Cell Biology | volume = 16 | issue = 3 | pages = 322–7 | date = June 2004 | pmid = 15145358 | doi = 10.1016/j.ceb.2004.03.009 | url = https://zenodo.org/record/1258830 | department = Review }}</ref>

===Nucleolus===
{{Main|Nucleolus}}
{{Further|Nuclear bodies}}
[[Image:Micrograph of a cell nucleus.png|thumb|200px|An [[electron micrograph]] of a cell nucleus, showing the darkly stained [[nucleolus]]]]

The [[nucleolus]] is the largest of the discrete densely stained, membraneless structures known as [[nuclear bodies]] found in the nucleus. It forms around [[tandem repeat]]s of [[ribosomal DNA|rDNA]], DNA coding for [[ribosomal RNA]] (rRNA). These regions are called [[nucleolar organizer regions]] (NOR). The main roles of the nucleolus are to synthesize rRNA and [[Nucleolus#Function and ribosome assembly|assemble ribosomes]]. The structural cohesion of the nucleolus depends on its activity, as ribosomal assembly in the nucleolus results in the transient association of nucleolar components, facilitating further ribosomal assembly, and hence further association. This model is supported by observations that inactivation of rDNA results in intermingling of nucleolar structures.<ref name="Hernandez-Verdun">{{cite journal | vauthors = Hernandez-Verdun D | title = Nucleolus: from structure to dynamics | journal = Histochemistry and Cell Biology | volume = 125 | issue = 1–2 | pages = 127–37 | date = January 2006 | pmid = 16328431 | doi = 10.1007/s00418-005-0046-4 | url = https://hal.archives-ouvertes.fr/hal-00015455 | s2cid = 20769260 | department = Review }}</ref>

In the first step of ribosome assembly,  a protein called [[RNA polymerase I]] transcribes rDNA, which forms a large pre-rRNA precursor. This is cleaved into two [[LSU rRNA|large rRNA subunits]] – [[5.8S ribosomal RNA|5.8S]], and [[28S ribosomal RNA|28S]], and a [[SSU rRNA|small rRNA subunit]] [[18S ribosomal RNA|18S]].<ref name=Alberts2015/>{{rp|328}}<ref name="Lamond-Sleeman">{{cite journal | vauthors = Lamond AI, Sleeman JE | title = Nuclear substructure and dynamics | journal = Current Biology | volume = 13 | issue = 21 | pages = R825-8 | date = October 2003 | pmid = 14588256 | doi = 10.1016/j.cub.2003.10.012 | s2cid = 16865665 | department = Review | doi-access = free | bibcode = 2003CBio...13.R825L }}</ref> The transcription, post-transcriptional processing, and assembly of rRNA occurs in the nucleolus, aided by [[small nucleolar RNA]] (snoRNA) molecules, some of which are derived from spliced [[intron]]s from [[messenger RNA]]s encoding genes related to ribosomal function. The assembled ribosomal subunits are the largest structures passed through the [[nuclear pore]]s.<ref name="Lodish" />{{rp|526}}

When observed under the [[electron microscope]], the nucleolus can be seen to consist of three distinguishable regions: the innermost ''fibrillar centers'' (FCs), surrounded by the ''dense fibrillar component'' (DFC) (that contains [[fibrillarin]] and [[nucleolin]]), which in turn is bordered by the ''granular component'' (GC) (that contains the protein [[nucleophosmin]]). Transcription of the rDNA occurs either in the FC or at the FC-DFC boundary, and, therefore, when rDNA transcription in the cell is increased, more FCs are detected. Most of the cleavage and modification of rRNAs occurs in the DFC, while the latter steps involving protein assembly onto the ribosomal subunits occur in the GC.<ref name=Lamond-Sleeman />

==={{anchor|Splicing speckles}} Splicing speckles===

Speckles are subnuclear structures that are enriched in pre-messenger RNA splicing factors and are located in the interchromatin regions of the nucleoplasm of mammalian cells.<ref>
{{cite journal | vauthors = Spector DL, Lamond AI | title = Nuclear speckles | journal = Cold Spring Harbor Perspectives in Biology | volume = 3 | issue = 2 | pages = a000646 | date = Feb 2011 | pmid = 20926517 | pmc = 3039535 | doi = 10.1101/cshperspect.a000646 | department = Review }}</ref>
At the fluorescence-microscope level they appear as irregular, punctate structures, which vary in size and shape, and when examined by electron microscopy they are seen as clusters of [[interchromatin granules]]. Speckles are dynamic structures, and both their protein and RNA-protein components can cycle continuously between speckles and other nuclear locations, including active transcription sites. Speckles can work with [[p53]] as enhancers of gene activity to directly enhance the activity of certain genes. Moreover, speckle-associating and non-associating p53 gene targets are functionally distinct.<ref>
{{cite journal | vauthors = Alexander KA, Coté A, Nguyen SC, Zhang L, Berger SL | title = p53 mediates target gene association with nuclear speckles for amplified RNA expression | journal = Molecular Cell | volume =  81| issue =  8| pages = S1097-2765(21)00174-X | date = Mar 2021 | pmid = 33823140 | pmc =  8830378| doi = 10.1016/j.molcel.2021.03.006 | s2cid = 233172170 | department = Primary }}</ref>

Studies on the composition, structure and behaviour of speckles have provided a model for understanding the functional compartmentalization of the nucleus and the organization of the gene-expression machinery<ref name="ReferenceA">{{cite journal | vauthors = Lamond AI, Spector DL | title = Nuclear speckles: a model for nuclear organelles | journal = Nature Reviews. Molecular Cell Biology | volume = 4 | issue = 8 | pages = 605–12 | date = August 2003 | pmid = 12923522 | doi = 10.1038/nrm1172 | s2cid = 6439413 | department = Review }}</ref> splicing [[snRNP]]s<ref>{{cite journal | vauthors = Tripathi K, Parnaik VK | title = Differential dynamics of splicing factor SC35 during the cell cycle | journal = Journal of Biosciences | volume = 33 | issue = 3 | pages = 345–54 | date = September 2008 | pmid = 19005234 | doi = 10.1007/s12038-008-0054-3 | url = http://www.ias.ac.in/jbiosci/sep2008/345.pdf | url-status = live | s2cid = 6332495 | department = Primary | archive-url = https://web.archive.org/web/20111115235056/http://www.ias.ac.in/jbiosci/sep2008/345.pdf | archive-date = 15 November 2011 }}</ref><ref>{{cite journal | vauthors = Tripathi K, Parnaik VK | title = Differential dynamics of splicing factor SC35 during the cell cycle | journal = Journal of Biosciences | volume = 33 | issue = 3 | pages = 345–54 | date = September 2008 | pmid = 19005234 | doi = 10.1007/s12038-008-0054-3 | s2cid = 6332495 | department = Primary }}</ref> and other splicing proteins necessary for pre-mRNA processing.<ref name="ReferenceA"/> Because of a cell's changing requirements, the composition and location of these bodies changes according to mRNA transcription and regulation via [[phosphorylation]] of specific proteins.<ref name="Handwerger">{{cite journal | vauthors = Handwerger KE, Gall JG | title = Subnuclear organelles: new insights into form and function | journal = Trends in Cell Biology | volume = 16 | issue = 1 | pages = 19–26 | date = January 2006 | pmid = 16325406 | doi = 10.1016/j.tcb.2005.11.005 | department = Review }}</ref> The splicing speckles are also known as nuclear speckles (nuclear specks), splicing factor compartments (SF compartments), interchromatin granule clusters (IGCs), and [[snurposome|B snurposomes]].<ref>{{cite web | title = Cellular component Nucleus speckle | publisher = UniProt: UniProtKB | url = https://www.uniprot.org/locations/SL-0186 | access-date = 30 August 2013}}</ref>
B snurposomes are found in the amphibian oocyte nuclei and in ''[[Drosophila melanogaster]]'' embryos. B snurposomes appear alone or attached to the Cajal bodies in the electron micrographs of the amphibian nuclei.<ref>
{{cite journal | vauthors = Gall JG, Bellini M, Wu Z, Murphy C | title = Assembly of the nuclear transcription and processing machinery: Cajal bodies (coiled bodies) and transcriptosomes | journal = Molecular Biology of the Cell | volume = 10 | issue = 12 | pages = 4385–402 | date = December 1999 | pmid = 10588665 | pmc = 25765 | doi = 10.1091/mbc.10.12.4385 | department = Primary }}</ref> While nuclear speckles were originally thought to be storage sites for the splicing factors,<ref name="Matera2007_NatureMolCellBio">{{cite journal | vauthors = Matera AG, Terns RM, Terns MP | title = Non-coding RNAs: lessons from the small nuclear and small nucleolar RNAs | journal = Nature Reviews. Molecular Cell Biology | volume = 8 | issue = 3 | pages = 209–20 | date = March 2007 | pmid = 17318225 | doi = 10.1038/nrm2124 | s2cid = 30268055 | department = Review }}</ref> a more recent study demonstrated that organizing genes and pre-mRNA substrates near speckles increases the kinetic efficiency of pre-mRNA splicing, ultimately boosting protein levels by modulation of splicing.<ref>{{cite journal | vauthors = Bhat P, Chow A, Emert B et al | title = Genome organization around nuclear speckles drives mRNA splicing efficiency. | journal = Nature | volume = 629 | issue = 5 | pages = 1165–1173 | date = May 2024 | pmid = 38720076 | pmc = 11164319 | doi = 10.1038/s41586-024-07429-6 | bibcode = 2024Natur.629.1165B }}</ref>

===Cajal bodies and gems===
[[File:Cajal-Body-Overview.svg|thumb|Cajal body]]
A nucleus typically contains between one and ten compact structures called [[Cajal body|Cajal bodies]] or coiled bodies (CB), whose diameter measures between 0.2&nbsp;μm and 2.0&nbsp;μm depending on the cell type and species.<ref name="Cioce" /> When seen under an electron microscope, they resemble balls of tangled thread<ref name="Pollard" /> and are dense foci of distribution for the protein [[coilin]].<ref name="MateraFrey">{{cite journal | vauthors = Matera AG, Frey MR | title = Coiled bodies and gems: Janus or gemini? | journal = American Journal of Human Genetics | volume = 63 | issue = 2 | pages = 317–21 | date = August 1998 | pmid = 9683623 | pmc = 1377332 | doi = 10.1086/301992 | department = Review }}</ref> CBs are involved in a number of different roles relating to RNA processing, specifically [[snoRNA|small nucleolar RNA]] (snoRNA) and [[small nuclear RNA]] (snRNA) maturation, and histone mRNA modification.<ref name="Cioce" />

Similar to Cajal bodies are Gemini of Cajal bodies, or gems, whose name is derived from the [[Gemini (constellation)|Gemini constellation]] in reference to their close "twin" relationship with CBs. Gems are similar in size and shape to CBs, and in fact are virtually indistinguishable under the microscope.<ref name="MateraFrey" /> Unlike CBs, gems do not contain [[snRNP|small nuclear ribonucleoproteins]] (snRNPs), but do contain a protein called [[survival of motor neuron protein|survival of motor neuron]] (SMN) whose function relates to snRNP biogenesis. Gems are believed to assist CBs in snRNP biogenesis,<ref name="Matera">{{cite journal | vauthors = Matera AG | title = Of coiled bodies, gems, and salmon | journal = Journal of Cellular Biochemistry | volume = 70 | issue = 2 | pages = 181–92 | date = August 1998 | pmid = 9671224 | doi = 10.1002/(sici)1097-4644(19980801)70:2<181::aid-jcb4>3.0.co;2-k | s2cid = 44941483 | department = Review }}</ref> though it has also been suggested from microscopy evidence that CBs and gems are different manifestations of the same structure.<ref name="MateraFrey" /> Later ultrastructural studies have shown gems to be twins of Cajal bodies with the difference being in the coilin component; Cajal bodies are SMN positive and coilin positive, and gems are SMN positive and coilin negative.<ref name="Navascues">{{cite journal | vauthors = Navascues J, Berciano MT, Tucker KE, Lafarga M, Matera AG | title = Targeting SMN to Cajal bodies and nuclear gems during neuritogenesis | journal = Chromosoma | volume = 112 | issue = 8 | pages = 398–409 | date = June 2004 | pmid = 15164213 | pmc = 1592132 | doi = 10.1007/s00412-004-0285-5 | department = Primary }}</ref>

===Other nuclear bodies===

{{main|Nuclear bodies}}

{| class="wikitable" style="float:right; font-size:100%; margin-left:15px;"
|- bgcolor="#efefef"
|+ '''Subnuclear structure sizes'''
|- bgcolor="#efefef"
! style="width: 120px" abbr="name"     |'''Structure name'''
! style="width: 130px" abbr="diameter" |'''Structure diameter'''
! scope="col" | {{nowrap|{{Abbr|Ref.|Reference}}}}
|-
| Cajal bodies || 0.2–2.0&nbsp;μm || <ref name="Cioce">{{cite journal | vauthors = Cioce M, Lamond AI | title = Cajal bodies: a long history of discovery | journal = Annual Review of Cell and Developmental Biology | volume = 21 | pages = 105–31 | year = 2005 | pmid = 16212489 | doi = 10.1146/annurev.cellbio.20.010403.103738 | s2cid = 8807316 | department = Review }}</ref>
|-
|Clastosomes 
|0.2–0.5&nbsp;μm
|<ref name="Lafarga-2002" />
|-
| PIKA || 5&nbsp;μm || <ref name="Pollard">{{cite book | last1 = Pollard | first1 = Thomas D. | first2 = William C. | last2 = Earnshaw | name-list-style = vanc | title = Cell Biology | publisher = Saunders | year = 2004 | location = Philadelphia | isbn = 978-0-7216-3360-2 | url-access = registration | url = https://archive.org/details/cellbiology0000poll }}</ref>
|-
| PML bodies || 0.2–1.0&nbsp;μm || <ref name="Dundr">{{cite journal | vauthors = Dundr M, Misteli T | title = Functional architecture in the cell nucleus | journal = The Biochemical Journal | volume = 356 | issue = Pt 2 | pages = 297–310 | date = June 2001 | pmid = 11368755 | pmc = 1221839 | doi = 10.1042/0264-6021:3560297 | department = Review }}</ref>
|-
| Paraspeckles || 0.5–1.0&nbsp;μm || <ref>{{cite journal | vauthors = Bond CS, Fox AH | title = Paraspeckles: nuclear bodies built on long noncoding RNA | journal = The Journal of Cell Biology | volume = 186 | issue = 5 | pages = 637–44 | date = September 2009 | pmid = 19720872 | pmc = 2742191 | doi = 10.1083/jcb.200906113 | department = Review }}</ref>
|-
| Speckles || 20–25&nbsp;nm || <ref name="Pollard" />
|}
Beyond the nuclear bodies first described by [[Santiago Ramón y Cajal]] above (e.g., nucleolus, nuclear speckles, Cajal bodies) the nucleus contains a number of other nuclear bodies. These include polymorphic interphase karyosomal association (PIKA), promyelocytic leukaemia (PML) bodies, and [[paraspeckle]]s. Although little is known about a number of these domains, they are significant in that they show that the nucleoplasm is not a uniform mixture, but rather contains organized functional subdomains.<ref name="Dundr" />

Other subnuclear structures appear as part of abnormal disease processes. For example, the presence of small intranuclear rods has been reported in some cases of [[nemaline myopathy]]. This condition typically results from mutations in [[actin]], and the rods themselves consist of mutant actin as well as other cytoskeletal proteins.<ref name="Goebel">{{cite journal | vauthors = Goebel HH, Warlo I | title = Nemaline myopathy with intranuclear rods--intranuclear rod myopathy | journal = Neuromuscular Disorders | volume = 7 | issue = 1 | pages = 13–9 | date = January 1997 | pmid = 9132135 | doi = 10.1016/S0960-8966(96)00404-X | s2cid = 29584217 | department = Review }}</ref>

====PIKA and PTF domains====
PIKA domains, or polymorphic interphase karyosomal associations, were first described in microscopy studies in 1991. Their function remains unclear, though they were not thought to be associated with active DNA replication, transcription, or RNA processing.<ref name="Saunders">{{cite journal | vauthors = Saunders WS, Cooke CA, Earnshaw WC | title = Compartmentalization within the nucleus: discovery of a novel subnuclear region | journal = The Journal of Cell Biology | volume = 115 | issue = 4 | pages = 919–31 | date = November 1991 | pmid = 1955462 | pmc = 2289954 | doi = 10.1083/jcb.115.4.919 | department = Primary }}</ref> They have been found to often associate with discrete domains defined by dense localization of the transcription factor PTF, which promotes transcription of [[small nuclear RNA]] (snRNA).<ref name="Pombo">{{cite journal | vauthors = Pombo A, Cuello P, Schul W, Yoon JB, Roeder RG, Cook PR, Murphy S | title = Regional and temporal specialization in the nucleus: a transcriptionally-active nuclear domain rich in PTF, Oct1 and PIKA antigens associates with specific chromosomes early in the cell cycle | journal = The EMBO Journal | volume = 17 | issue = 6 | pages = 1768–78 | date = March 1998 | pmid = 9501098 | pmc = 1170524 | doi = 10.1093/emboj/17.6.1768 | department = Primary }}</ref>

====PML-nuclear bodies====
[[Promyelocytic leukemia protein]] (PML-nuclear bodies) are spherical bodies found scattered throughout the nucleoplasm, measuring around 0.1–1.0&nbsp;μm. They are known by a number of other names, including nuclear domain 10 (ND10), Kremer bodies, and PML oncogenic domains.<ref name="Zimber">{{cite journal | vauthors = Zimber A, Nguyen QD, Gespach C | title = Nuclear bodies and compartments: functional roles and cellular signalling in health and disease | journal = Cellular Signalling | volume = 16 | issue = 10 | pages = 1085–104 | date = October 2004 | pmid = 15240004 | doi = 10.1016/j.cellsig.2004.03.020 | department = Review }}</ref> PML-nuclear bodies are named after one of their major components, the promyelocytic leukemia protein (PML). They are often seen in the nucleus in association with Cajal bodies and cleavage bodies.<ref name="Dundr"/> Pml-/- mice, which are unable to create PML-nuclear bodies, develop normally without obvious ill effects, showing that PML-nuclear bodies are not required for most essential biological processes.<ref name="Lallemand2010">{{cite journal | vauthors = Lallemand-Breitenbach V, de Thé H | title = PML nuclear bodies | journal = Cold Spring Harbor Perspectives in Biology | volume = 2 | issue = 5 | pages = a000661 | date = May 2010 | pmid = 20452955 | pmc = 2857171 | doi = 10.1101/cshperspect.a000661 | department = Review }}</ref>

====Paraspeckles====
{{Main|Paraspeckle}}
Discovered by Fox et al. in 2002, paraspeckles are irregularly shaped compartments in the interchromatin space of the nucleus.<ref name="Fox_2010">{{cite journal | vauthors = Fox AH, Lamond AI | title = Paraspeckles | journal = Cold Spring Harbor Perspectives in Biology | volume = 2 | issue = 7 | pages = a000687 | date = July 2010 | pmid = 20573717 | pmc = 2890200 | doi = 10.1101/cshperspect.a000687 | department = Review }}</ref>  First documented in HeLa cells, where there are generally 10–30 per nucleus,<ref name="para2">{{cite web | last1 =Fox | first1 =Archa | first2 = Wendy | last2 = Bickmore | name-list-style = vanc | title = Nuclear Compartments: Paraspeckles | publisher = Nuclear Protein Database | year = 2004 | url =http://npd.hgu.mrc.ac.uk/compartments/paraspeckles.html | archive-url = http://webarchive.nationalarchives.gov.uk/20080910110920/http://npd.hgu.mrc.ac.uk/compartments/paraspeckles.html | url-status =dead | archive-date =10 September 2008 | access-date = 6 March 2007 }}</ref> paraspeckles are now known to also exist in all human primary cells, transformed cell lines, and tissue sections.<ref name="para3">{{cite journal | vauthors = Fox AH, Bond CS, Lamond AI | title = P54nrb forms a heterodimer with PSP1 that localizes to paraspeckles in an RNA-dependent manner | journal = Molecular Biology of the Cell | volume = 16 | issue = 11 | pages = 5304–15 | date = November 2005 | pmid = 16148043 | pmc = 1266428 | doi = 10.1091/mbc.E05-06-0587 | department = Primary }}</ref> Their name is derived from their distribution in the nucleus; the "para" is short for parallel and the "speckles" refers to the splicing speckles to which they are always in close proximity.<ref name="para2"/>

Paraspeckles sequester nuclear proteins and RNA and thus appear to function as a molecular sponge<ref name="Nakagawa_2018">{{cite journal | vauthors = Nakagawa S, Yamazaki T, Hirose T | title = Molecular dissection of nuclear paraspeckles: towards understanding the emerging world of the RNP milieu | journal = Open Biology | volume = 8 | issue = 10 | date = October 2018 | page = 180150 | pmid = 30355755 | pmc = 6223218 | doi = 10.1098/rsob.180150 | department = Review }}</ref> that is involved in the regulation of gene expression.<ref name="Pisani_2019">{{cite journal | vauthors = Pisani G, Baron B | title = Nuclear paraspeckles function in mediating gene regulatory and apoptotic pathways | journal = Non-Coding RNA Research | volume = 4 | issue = 4 | pages = 128–134 | date = December 2019 | pmid = 32072080 | pmc = 7012776 | doi = 10.1016/j.ncrna.2019.11.002 | department = Review }}</ref> Furthermore, paraspeckles are dynamic structures that are altered in response to changes in cellular metabolic activity. They are transcription dependent<ref name="Fox_2010" /> and in the absence of RNA Pol II transcription, the paraspeckle disappears and all of its associated protein components  (PSP1, p54nrb, PSP2, CFI(m)68, and PSF) form a crescent shaped perinucleolar cap in the nucleolus. This phenomenon is demonstrated during the cell cycle. In the [[cell cycle]], paraspeckles are present during [[interphase]] and during all of [[mitosis]] except for [[telophase]]. During telophase, when the two daughter nuclei are formed, there is no [[RNA]] Pol II [[Transcription (genetics)|transcription]] so the protein components instead form a perinucleolar cap.<ref name="para3"/>

===={{anchor|Perichromatin fibrils}} Perichromatin fibrils====

Perichromatin fibrils are visible only under electron microscope. They are located next to the transcriptionally active chromatin and are hypothesized to be the sites of active [[precursor mRNA|pre-mRNA]] processing.<ref name="Matera2007_NatureMolCellBio" />

====Clastosomes====

Clastosomes are small nuclear bodies (0.2–0.5&nbsp;μm) described as having a thick ring-shape due to the peripheral capsule around these bodies.<ref name="Lafarga-2002">{{cite journal | vauthors = Lafarga M, Berciano MT, Pena E, Mayo I, Castaño JG, Bohmann D, Rodrigues JP, Tavanez JP, Carmo-Fonseca M | display-authors = 6 | title = Clastosome: a subtype of nuclear body enriched in 19S and 20S proteasomes, ubiquitin, and protein substrates of proteasome | journal = Molecular Biology of the Cell | volume = 13 | issue = 8 | pages = 2771–82 | date = August 2002 | pmid = 12181345 | pmc = 117941 | doi = 10.1091/mbc.e02-03-0122 | citeseerx = 10.1.1.321.6138 | department = Primary }}</ref> This name is derived from the Greek ''klastos'' ([[wikt:κλαστός|κλαστός]]), broken and ''soma'' ([[wikt:σῶμα|σῶμα]]), body.<ref name="Lafarga-2002" /> Clastosomes are not typically present in normal cells, making them hard to detect. They form under high [[Proteolysis|proteolytic]] conditions within the nucleus and degrade once there is a decrease in activity or if cells are treated with [[proteasome inhibitor]]s.<ref name="Lafarga-2002" /><ref>{{cite journal | vauthors = Kong XN, Yan HX, Chen L, Dong LW, Yang W, Liu Q, Yu LX, Huang DD, Liu SQ, Liu H, Wu MC, Wang HY | display-authors = 6 | title = LPS-induced down-regulation of signal regulatory protein {alpha} contributes to innate immune activation in macrophages | journal = The Journal of Experimental Medicine | volume = 204 | issue = 11 | pages = 2719–31 | date = October 2007 | pmid = 17954568 | pmc = 2118489 | doi = 10.1084/jem.20062611 | department = Primary }}</ref> The scarcity of clastosomes in cells indicates that they are not required for [[proteasome]] function.<ref name="Carmo-Fonseca-2010">{{cite journal | vauthors = Carmo-Fonseca M, Berciano MT, Lafarga M | title = Orphan nuclear bodies | journal = Cold Spring Harbor Perspectives in Biology | volume = 2 | issue = 9 | pages = a000703 | date = September 2010 | pmid = 20610547 | pmc = 2926751 | doi = 10.1101/cshperspect.a000703 | department = Review }}</ref> [[Osmotic shock|Osmotic stress]] has also been shown to cause the formation of clastosomes.<ref>{{cite journal | vauthors = Sampuda KM, Riley M, Boyd L | title = Stress induced nuclear granules form in response to accumulation of misfolded proteins in Caenorhabditis elegans | journal = BMC Cell Biology | volume = 18 | issue = 1 | pages = 18 | date = April 2017 | pmid = 28424053 | pmc = 5395811 | doi = 10.1186/s12860-017-0136-x | department = Primary | doi-access = free }}</ref> These nuclear bodies contain catalytic and regulatory subunits of the proteasome and its substrates, indicating that clastosomes are sites for degrading proteins.<ref name="Carmo-Fonseca-2010" />

== Function ==
The nucleus provides a site for [[Transcription (biology)|genetic transcription]] that is segregated from the location of [[translation (biology)|translation]] in the cytoplasm, allowing levels of [[gene regulation]] that are not available to [[prokaryote]]s. The main function of the cell nucleus is to control [[gene expression]] and mediate the [[DNA replication|replication of DNA]] during the cell cycle.<ref name = "Lodish" />{{rp|171}}

===Cell compartmentalization===
The [[nuclear envelope]] allows control of the nuclear contents, and separates them from the rest of the cytoplasm where necessary. This is important for controlling processes on either side of the nuclear membrane: In most cases where a cytoplasmic process needs to be restricted, a key participant is removed to the nucleus, where it interacts with transcription factors to downregulate the production of certain enzymes in the pathway. This regulatory mechanism occurs in the case of [[glycolysis]], a cellular pathway for breaking down [[glucose]] to produce energy. [[Hexokinase]] is an enzyme responsible for the first step of glycolysis, forming [[glucose-6-phosphate]] from glucose. At high concentrations of [[fructose-6-phosphate]], a molecule made later from glucose-6-phosphate, a regulator protein removes hexokinase to the nucleus,<ref name="Lehninger">{{cite book | last1 =Lehninger | first1 =Albert L. | last2 =Nelson | first2 =David L. | last3 =Cox | first3 =Michael M. | name-list-style =vanc | title =Lehninger principles of biochemistry | edition =3rd | year =2000 | publisher =Worth Publishers | location =New York | isbn =978-1-57259-931-4 | url-access =registration | url =https://archive.org/details/lehningerprincip01lehn }}</ref> where it forms a transcriptional repressor complex with nuclear proteins to reduce the expression of genes involved in glycolysis.<ref name="Moreno">{{cite journal | vauthors = Moreno F, Ahuatzi D, Riera A, Palomino CA, Herrero P | title = Glucose sensing through the Hxk2-dependent signalling pathway | journal = Biochemical Society Transactions | volume = 33 | issue = Pt 1 | pages = 265–8 | date = February 2005 | pmid = 15667322 | doi = 10.1042/BST0330265 | s2cid = 20647022 | department = Primary }}</ref>

In order to control which genes are being transcribed, the cell separates some transcription factor proteins responsible for regulating gene expression from physical access to the DNA until they are activated by other signaling pathways. This prevents even low levels of inappropriate gene expression. For example, in the case of [[NF-κB]]-controlled genes, which are involved in most [[inflammation|inflammatory]] responses, transcription is induced in response to a [[cell signaling|signal pathway]] such as that initiated by the signaling molecule [[TNF-α]], binds to a cell membrane receptor, resulting in the recruitment of signalling proteins, and eventually activating the transcription factor NF-κB. A [[nuclear localisation signal]] on the NF-κB protein allows it to be transported through the nuclear pore and into the nucleus, where it stimulates the transcription of the target genes.<ref name="MBoC" />

The compartmentalization allows the cell to prevent translation of unspliced mRNA.<ref name="Gorlich">{{cite journal | vauthors = Görlich D, Kutay U | title = Transport between the cell nucleus and the cytoplasm | journal = Annual Review of Cell and Developmental Biology | volume = 15 | issue = 1 | pages = 607–60 | year = 1999 | pmid = 10611974 | doi = 10.1146/annurev.cellbio.15.1.607 | department = Review }}</ref> Eukaryotic mRNA contains introns that must be removed before being translated to produce functional proteins. The splicing is done inside the nucleus before the mRNA can be accessed by ribosomes for translation. Without the nucleus, ribosomes would translate newly transcribed (unprocessed) mRNA, resulting in malformed and nonfunctional proteins.<ref name = "Lodish" />{{rp|108–15}}

===Replication===
{{Main|Eukaryotic DNA replication}}

The main function of the cell nucleus is to control gene expression and mediate the replication of DNA during the cell cycle.<ref name = "Lodish" />{{rp|171}} It has been found that replication happens in a localised way in the cell nucleus. In the S phase of interphase of the cell cycle; replication takes place. Contrary to the traditional view of moving replication forks along stagnant DNA, a concept of  ''replication factories'' emerged, which means replication forks are concentrated towards some immobilised 'factory' regions through which the template DNA strands pass like conveyor belts.<ref name="Hozák_1994">{{cite journal | vauthors = Hozák P, Cook PR | title = Replication factories | journal = Trends in Cell Biology | volume = 4 | issue = 2 | pages = 48–52 | date = February 1994 | pmid = 14731866 | doi = 10.1016/0962-8924(94)90009-4 | department = Review }}</ref>

===Gene expression===
{{Main|Gene expression}}
{{See also|Transcription factories}}
[[File:Basic diagram of a transcription factory during transcription.png|thumb|upright=1.3|A generic [[Transcription factories|transcription factory]] during transcription, highlighting the possibility of transcribing more than one gene at a time. The diagram includes 8 RNA polymerases however the number can vary depending on cell type. The image also includes transcription factors and a porous, protein core.]]

Gene expression first involves transcription, in which DNA is used as a template to produce RNA. In the case of genes encoding proteins, that RNA produced from this process is messenger RNA (mRNA), which then needs to be translated by ribosomes to form a protein. As ribosomes are located outside the nucleus, mRNA produced needs to be exported.<ref>{{cite book |title=Protein Synthesis and Ribosome Structure: Translating the Genome |last1=Nierhaus |first1=Knud H. | first2 = Daniel N. | last2 = Wilson | name-list-style = vanc |year=2004 |publisher=Wiley-VCH |isbn=978-3-527-30638-1 }}</ref>

Since the nucleus is the site of transcription, it also contains a variety of proteins that either directly mediate transcription or are involved in regulating the process. These proteins include [[helicase]]s, which unwind the double-stranded DNA molecule to facilitate access to it, [[RNA polymerase]]s, which bind to the DNA promoter to synthesize the growing RNA molecule, [[topoisomerase]]s, which change the amount of [[supercoil]]ing in DNA, helping it wind and unwind, as well as a large variety of transcription factors that regulate expression.<ref>{{cite book |title=Genome Structure and Function: From Chromosomes Characterization to Genes Technology |last=Nicolini |first=Claudio A. | name-list-style = vanc |year=1997 |publisher=Springer |isbn=978-0-7923-4565-7 }}</ref>

===Processing of pre-mRNA===
{{Main|Post-transcriptional modification}}
Newly synthesized mRNA molecules are known as [[primary transcript]]s or pre-mRNA. They must undergo [[post-transcriptional modification]] in the nucleus before being exported to the cytoplasm; mRNA that appears in the cytoplasm without these modifications is degraded rather than used for protein translation. The three main modifications are [[5' cap]]ping, 3' [[polyadenylation]], and [[RNA splicing]]. While in the nucleus, pre-mRNA is associated with a variety of proteins in complexes known as [[heterogeneous ribonucleoprotein particle]]s (hnRNPs). Addition of the 5' cap occurs co-transcriptionally and is the first step in post-transcriptional modification. The 3' poly-[[adenine]] tail is only added after transcription is complete.<ref name = "Lodish" />{{rp|509–18}}

RNA splicing, carried out by a complex called the [[spliceosome]], is the process by which introns, or regions of DNA that do not code for protein, are removed from the pre-mRNA and the remaining [[exon]]s connected to re-form a single continuous molecule. This process normally occurs after 5' capping and 3' polyadenylation but can begin before synthesis is complete in transcripts with many exons.<ref name="Lodish" />{{rp|494}} Many pre-mRNAs can be spliced in multiple ways to produce different mature mRNAs that encode different [[primary structure|protein sequences]]. This process is known as [[alternative splicing]], and allows production of a large variety of proteins from a limited amount of DNA.<ref name=Black>{{cite journal | vauthors = Black DL | title = Mechanisms of alternative pre-messenger RNA splicing | journal = Annual Review of Biochemistry | volume = 72 | issue = 1 | pages = 291–336 | year = 2003 | pmid = 12626338 | doi = 10.1146/annurev.biochem.72.121801.161720 | s2cid = 23576288 | url = https://cloudfront.escholarship.org/dist/prd/content/qt2hg605wm/qt2hg605wm.pdf  | department = Review }}</ref>
{{Clear}}

==Dynamics and regulation==

===Nuclear transport===
{{Main|Nuclear transport}}

[[Image:RanGTPcycle.png|360px|right|thumb|[[Macromolecule]]s, such as [[RNA]] and [[protein]]s, are [[active transport|actively transported]] across the nuclear membrane in a process called the [[Ran (biology)|Ran]]-[[Guanosine triphosphate|GTP]] nuclear transport cycle.]]

The entry and exit of large molecules from the nucleus is tightly controlled by the nuclear pore complexes. Although small molecules can enter the nucleus without regulation,<ref name="Watson">{{cite book | vauthors = Watson JD, Baker TA, Bell SP, Gann A, Levine M, Losick R | title = Molecular Biology of the Gene | publisher = Peason Benjamin Cummings; CSHL Press. | year = 2004 | edition = 5th | chapter = Ch9–10 | isbn = 978-0-8053-9603-4 }}</ref> macromolecules such as RNA and proteins require association karyopherins called [[importin]]s to enter the nucleus and [[exportin]]s to exit. "Cargo" proteins that must be translocated from the cytoplasm to the nucleus contain short amino acid sequences known as [[nuclear localization signal]]s, which are bound by importins, while those transported from the nucleus to the cytoplasm carry [[nuclear export signal]]s bound by exportins. The ability of importins and exportins to transport their cargo is regulated by [[GTPase]]s, enzymes that [[Hydrolysis|hydrolyze]] the molecule guanosine triphosphate (GTP) to release energy. The key GTPase in nuclear transport is [[Ran (protein)|Ran]], which is bound to either GTP or GDP (guanosine diphosphate), depending on whether it is located in the nucleus or the cytoplasm. Whereas importins depend on RanGTP to dissociate from their cargo, exportins require RanGTP in order to bind to their cargo.<ref name="Pemberton" />

Nuclear import depends on the importin binding its cargo in the cytoplasm and carrying it through the nuclear pore into the nucleus. Inside the nucleus, RanGTP acts to separate the cargo from the importin, allowing the importin to exit the nucleus and be reused. Nuclear export is similar, as the exportin binds the cargo inside the nucleus in a process facilitated by RanGTP, exits through the nuclear pore, and separates from its cargo in the cytoplasm.<ref name="Cavazza_2015">{{cite journal | vauthors = Cavazza T, Vernos I | title = The RanGTP Pathway: From Nucleo-Cytoplasmic Transport to Spindle Assembly and Beyond | journal = Frontiers in Cell and Developmental Biology | volume = 3 | pages = 82 | date = 2015 | pmid = 26793706 | pmc = 4707252 | doi = 10.3389/fcell.2015.00082 | department = Review | doi-access = free }}</ref>

Specialized export proteins exist for translocation of mature mRNA and tRNA to the cytoplasm after post-transcriptional modification is complete. This quality-control mechanism is important due to these molecules' central role in protein translation. Mis-expression of a protein due to incomplete excision of exons or mis-incorporation of amino acids could have negative consequences for the cell; thus, incompletely modified RNA that reaches the cytoplasm is degraded rather than used in translation.<ref name="Lodish" />

===Assembly and disassembly===
[[File:Mitosis-fluorescent.jpg|thumb|230px|An image of a [[newt]] [[lung]] cell [[staining (biology)|stained]] with [[fluorescent]] [[dye]]s during [[metaphase]]. The [[mitotic spindle]] can be seen, stained green, attached to the two sets of [[chromosome]]s, stained light blue. All chromosomes but one are already at the metaphase plate. ]]

During its lifetime, a nucleus may be broken down or destroyed, either in the process of [[cell division]] or as a consequence of [[apoptosis]] (the process of [[programmed cell death]]). During these events, the structural components of the nucleus&nbsp;— the envelope and lamina&nbsp;— can be systematically degraded.
In most cells, the disassembly of the nuclear envelope marks the end of the [[prophase]] of mitosis. However, this disassembly of the nucleus is not a universal feature of mitosis and does not occur in all cells. Some unicellular eukaryotes (e.g., yeasts) undergo so-called [[closed mitosis]], in which the nuclear envelope remains intact. In closed mitosis, the daughter chromosomes migrate to opposite poles of the nucleus, which then divides in two. The cells of higher eukaryotes, however, usually undergo [[open mitosis]], which is characterized by breakdown of the nuclear envelope. The daughter chromosomes then migrate to opposite poles of the mitotic spindle, and new nuclei reassemble around them.<ref name = "Lodish" />{{rp|854}}

At a certain point during the cell cycle in open mitosis, the cell divides to form two cells. In order for this process to be possible, each of the new daughter cells must have a full set of genes, a process requiring replication of the chromosomes as well as segregation of the separate sets. This occurs by the replicated chromosomes, the [[sister chromatid]]s, attaching to [[microtubule]]s, which in turn are attached to different [[centrosome]]s. The sister chromatids can then be pulled to separate locations in the cell. In many cells, the centrosome is located in the cytoplasm, outside the nucleus; the microtubules would be unable to attach to the chromatids in the presence of the nuclear envelope.<ref name="Lippincott-Schwartz">{{cite journal | vauthors = Lippincott-Schwartz J | title = Cell biology: ripping up the nuclear envelope | journal = Nature | volume = 416 | issue = 6876 | pages = 31–2 | date = March 2002 | pmid = 11882878 | doi = 10.1038/416031a | url = https://zenodo.org/record/1233215 | s2cid = 4431000 | department = Commentary | bibcode = 2002Natur.416...31L | doi-access = free }}</ref> Therefore, the early stages in the cell cycle, beginning in prophase and until around [[prometaphase]], the nuclear membrane is dismantled.<ref name="RGoldman" /> Likewise, during the same period, the nuclear lamina is also disassembled, a process regulated by phosphorylation of the lamins by protein kinases such as the [[CDC2|CDC2 protein kinase]].<ref name="Boulikas">{{cite journal | vauthors = Boulikas T | title = Phosphorylation of transcription factors and control of the cell cycle | journal = Critical Reviews in Eukaryotic Gene Expression | volume = 5 | issue = 1 | pages = 1–77 | year = 1995 | pmid = 7549180 | department = Review }}</ref> Towards the end of the cell cycle, the nuclear membrane is reformed, and around the same time, the nuclear lamina are reassembled by dephosphorylating the lamins.<ref name="Boulikas" />

However, in [[dinoflagellates]], the nuclear envelope remains intact, the centrosomes are located in the cytoplasm, and the microtubules come in contact with chromosomes, whose centromeric regions are incorporated into the nuclear envelope (the so-called closed mitosis with extranuclear spindle). In many other protists (e.g., [[ciliate]]s, [[Apicomplexa|sporozoans]]) and fungi, the centrosomes are intranuclear, and their nuclear envelope also does not disassemble during cell division.<ref name="Boettcher_2013">{{cite journal | vauthors = Boettcher B, Barral Y | title = The cell biology of open and closed mitosis | journal = Nucleus | location = Austin, Tex. | volume = 4 | issue = 3 | pages = 160–5 | date = 2013 | pmid = 23644379 | pmc = 3720745 | doi = 10.4161/nucl.24676 | department = Review }}</ref>

Apoptosis is a controlled process in which the cell's structural components are destroyed, resulting in death of the cell. Changes associated with apoptosis directly affect the nucleus and its contents, for example, in the condensation of chromatin and the disintegration of the nuclear envelope and lamina. The destruction of the lamin networks is controlled by specialized apoptotic [[protease]]s called [[caspase]]s, which cleave the lamin proteins and, thus, degrade the nucleus' structural integrity. Lamin cleavage is sometimes used as a laboratory indicator of caspase activity in [[assay]]s for early apoptotic activity.<ref name="RGoldman" /> Cells that express mutant caspase-resistant lamins are deficient in nuclear changes related to apoptosis, suggesting that lamins play a role in initiating the events that lead to apoptotic degradation of the nucleus.<ref name="RGoldman" /> Inhibition of lamin assembly itself is an inducer of apoptosis.<ref name="Steen">{{cite journal | vauthors = Steen RL, Collas P | title = Mistargeting of B-type lamins at the end of mitosis: implications on cell survival and regulation of lamins A/C expression | journal = The Journal of Cell Biology | volume = 153 | issue = 3 | pages = 621–6 | date = April 2001 | pmid = 11331311 | pmc = 2190567 | doi = 10.1083/jcb.153.3.621 | department = Primary }}</ref>

The nuclear envelope acts as a barrier that prevents both DNA and RNA viruses from entering the nucleus. Some viruses require access to proteins inside the nucleus in order to replicate and/or assemble. DNA viruses, such as [[herpesvirus]] replicate and assemble in the cell nucleus, and exit by budding through the inner nuclear membrane. This process is accompanied by disassembly of the lamina on the nuclear face of the inner membrane.<ref name="RGoldman" />

===Disease-related dynamics===
Initially, it has been suspected that [[immunoglobulins]] in general and [[autoantibodies]] in particular do not enter the nucleus. Now there is a body of evidence that under pathological conditions (e.g. [[lupus erythematosus]]) IgG can enter the nucleus.<ref name="pmid17364135">{{cite journal | vauthors = Böhm I | title = IgG deposits can be detected in cell nuclei of patients with both lupus erythematosus and malignancy | journal = Clinical Rheumatology | volume = 26 | issue = 11 | pages = 1877–82 | date = November 2007 | pmid = 17364135 | doi = 10.1007/s10067-007-0597-y | s2cid = 44879431 | department = Primary }}</ref>

==Nuclei per cell==

Most [[eukaryotic]] cell types usually have a single nucleus, but some have no nuclei, while others have several. This can result from normal development, as in the maturation of mammalian [[red blood cell]]s, or from faulty cell division.<ref>{{cite book |last1=Ressel |first1=Lorenzo | name-list-style = vanc | chapter = Nuclear Morphologies |title=Normal cell morphology in canine and feline cytology: an identification guide |date=2017 |publisher=John Wiley & Sons |location=Hoboken, NJ |isbn=978-1-119-27891-7 |page=6 | chapter-url=https://books.google.com/books?id=AkwrDwAAQBAJ&pg=PA6}}</ref>

===Anucleated cells===

[[Image:redbloodcells.jpg|thumb|230px|right|Human red blood cells, like those of other mammals, lack nuclei. This occurs as a normal part of the cells' development.]]

An anucleated cell contains no nucleus and is, therefore, incapable of dividing to produce daughter cells. The best-known anucleated cell is the mammalian red blood cell, or [[erythrocyte]], which also lacks other organelles such as mitochondria, and serves primarily as a transport vessel to ferry [[oxygen]] from the [[lungs]] to the body's tissues. Erythrocytes mature through [[erythropoiesis]] in the [[bone marrow]], where they lose their nuclei, organelles, and ribosomes. The nucleus is expelled during the process of differentiation from an [[erythroblast]] to a [[reticulocyte]], which is the immediate precursor of the mature erythrocyte.<ref name="Skutelsky">{{cite journal | vauthors = Skutelsky E, Danon D | title = Comparative study of nuclear expulsion from the late erythroblast and cytokinesis | journal = Experimental Cell Research | volume = 60 | issue = 3 | pages = 427–36 | date = June 1970 | pmid = 5422968 | doi = 10.1016/0014-4827(70)90536-7 | department = Primary }}</ref> The presence of [[mutagen]]s may induce the release of some immature "micronucleated" erythrocytes into the bloodstream.<ref name="Torous">{{cite journal | vauthors = Torous DK, Dertinger SD, Hall NE, Tometsko CR | title = Enumeration of micronucleated reticulocytes in rat peripheral blood: a flow cytometric study | journal = Mutation Research | volume = 465 | issue = 1–2 | pages = 91–9 | date = February 2000 | pmid = 10708974 | doi = 10.1016/S1383-5718(99)00216-8 | bibcode = 2000MRGTE.465...91T | department = Primary }}</ref><ref name="Hutter">{{cite journal | vauthors = Hutter KJ, Stöhr M | title = Rapid detection of mutagen induced micronucleated erythrocytes by flow cytometry | journal = Histochemistry | volume = 75 | issue = 3 | pages = 353–62 | year = 1982 | pmid = 7141888 | doi = 10.1007/bf00496738 | s2cid = 28973947 | department = Primary }}</ref> Anucleated cells can also arise from flawed cell division in which one daughter lacks a nucleus and the other has two nuclei.

In [[flowering plant]]s, this condition occurs in [[sieve tube element]]s.<ref>{{cite journal | vauthors = Ham BK, Lucas WJ | title = The angiosperm phloem sieve tube system: a role in mediating traits important to modern agriculture | journal = Journal of Experimental Botany | volume = 65 | issue = 7 | pages = 1799–816 | date = April 2014 | pmid = 24368503 | doi = 10.1093/jxb/ert417 | doi-access = free }}</ref>

===Multinucleated cells===
{{Main|Multinucleate}}
[[Multinucleated]] cells contain multiple nuclei. Most [[acantharea]]n species of [[protozoa]]<ref name="Zettler">{{cite journal | vauthors = Zettler LA, Sogin ML, Caron DA | title = Phylogenetic relationships between the Acantharea and the Polycystinea: a molecular perspective on Haeckel's Radiolaria | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 21 | pages = 11411–6 | date = October 1997 | pmid = 9326623 | pmc = 23483 | doi = 10.1073/pnas.94.21.11411 | department = Primary | bibcode = 1997PNAS...9411411A | doi-access = free }}</ref> and some [[fungi]] in [[mycorrhizae]]<ref name="Horton">{{cite journal | vauthors = Horton TR | title = The number of nuclei in basidiospores of 63 species of ectomycorrhizal Homobasidiomycetes | journal = Mycologia | volume = 98 | issue = 2 | pages = 233–8 | year = 2006 | pmid = 16894968 | doi = 10.3852/mycologia.98.2.233 | department = Primary }}</ref> have naturally multinucleated cells. Other examples include the [[intestinal parasite]]s in the genus ''[[Giardia]]'', which have two nuclei per cell.<ref>{{cite journal | vauthors = Adam RD | title = The biology of Giardia spp | journal = Microbiological Reviews | volume = 55 | issue = 4 | pages = 706–32 | date = December 1991 | pmid = 1779932 | pmc = 372844 | doi = 10.1128/MMBR.55.4.706-732.1991 | department = Review }}</ref> [[Ciliate]]s have two kinds of nuclei in a single cell, a somatic [[macronucleus]] and a germline [[micronucleus]].<ref>{{cite journal |vauthors=Vogt A, Goldman AD, Mochizuki K, Landweber LF |title=Transposon Domestication versus Mutualism in Ciliate Genome Rearrangements |journal=PLOS Genetics |date=1 August 2013 |volume=9 |issue=8 |pages=e1003659 |doi=10.1371/journal.pgen.1003659 |pmid=23935529 |pmc=3731211 |doi-access=free }}</ref> In humans, [[Skeletal muscle#Skeletal muscle cells|skeletal muscle cells]], also called [[myocyte]]s and [[syncytium]], become multinucleated during development; the resulting arrangement of nuclei near the periphery of the cells allows maximal intracellular space for [[myofibrils]].<ref name="Lodish" /> Other multinucleate cells in the human are [[osteoclast]]s a type of [[bone cell]]. Multinucleated and [[binucleated cells]] can also be abnormal in humans; for example, cells arising from the fusion of [[monocyte]]s and [[macrophage]]s, known as [[giant multinucleated cell]]s, sometimes accompany inflammation<ref name="McInnes">{{cite journal | vauthors = McInnes A, Rennick DM | title = Interleukin 4 induces cultured monocytes/macrophages to form giant multinucleated cells | journal = The Journal of Experimental Medicine | volume = 167 | issue = 2 | pages = 598–611 | date = February 1988 | pmid = 3258008 | pmc = 2188835 | doi = 10.1084/jem.167.2.598 | department = Primary }}</ref> and are also implicated in tumor formation.<ref name="Goldring">{{cite journal | vauthors = Goldring SR, Roelke MS, Petrison KK, Bhan AK | title = Human giant cell tumors of bone identification and characterization of cell types | journal = The Journal of Clinical Investigation | volume = 79 | issue = 2 | pages = 483–91 | date = February 1987 | pmid = 3027126 | pmc = 424109 | doi = 10.1172/JCI112838 | department = Primary }}</ref>

A number of [[dinoflagellate]]s are known to have two nuclei. Unlike other multinucleated cells these nuclei contain two distinct lineages of DNA: one from the dinoflagellate and the other from a symbiotic [[diatom]].<ref name=Imanian2012>{{cite journal | vauthors = Imanian B, Pombert JF, Dorrell RG, Burki F, Keeling PJ | title = Tertiary endosymbiosis in two dinotoms has generated little change in the mitochondrial genomes of their dinoflagellate hosts and diatom endosymbionts | journal = PLOS ONE | volume = 7 | issue = 8 | pages = e43763 | year = 2012 | pmid = 22916303 | pmc = 3423374 | doi = 10.1371/journal.pone.0043763 | bibcode = 2012PLoSO...743763I | department = Primary | doi-access = free }}</ref>

==Evolution==
As the major defining characteristic of the eukaryotic cell, the nucleus's [[evolution]]ary origin has been the subject of much speculation. Four major hypotheses have been proposed to explain the existence of the nucleus, although none have yet earned widespread support.<ref name="Pennisi">{{cite journal | vauthors = Pennisi E | author-link = Elizabeth Pennisi | title = Evolutionary biology. The birth of the nucleus | journal = Science | volume = 305 | issue = 5685 | pages = 766–8 | date = August 2004 | pmid = 15297641 | doi = 10.1126/science.305.5685.766 | s2cid = 83769250 | department = News }}</ref><ref name="Devos_2014">{{cite journal | vauthors = Devos DP, Gräf R, Field MC | title = Evolution of the nucleus | journal = Current Opinion in Cell Biology | volume = 28 | pages = 8–15 | date = June 2014 | issue = 100 | pmid = 24508984 | pmc = 4071446 | doi = 10.1016/j.ceb.2014.01.004 | department = Review }}</ref><ref name="López-García_2015">{{cite journal | vauthors = López-García P, Moreira D | title = Open Questions on the Origin of Eukaryotes | journal = Trends in Ecology & Evolution | volume = 30 | issue = 11 | pages = 697–708 | date = November 2015 | pmid = 26455774 | pmc = 4640172 | doi = 10.1016/j.tree.2015.09.005 | bibcode = 2015TEcoE..30..697L | department = Review }}</ref>

The first model known as the "syntrophic model" proposes that a [[Symbiosis|symbiotic]] relationship between the [[archaea]] and [[bacteria]] created the nucleus-containing eukaryotic cell. (Organisms of the Archaeal and Bacterial domains have no cell nucleus.<ref>{{cite book | vauthors = Hogan CM | chapter = Archaea | title = Encyclopedia of Earth | veditors = Monosson E, Cleveland C | publisher = National Council for Science and the Environment | location = Washington, DC. | date = 2010 | archive-url = https://web.archive.org/web/20110511133400/http://www.eoearth.org/article/Archaea?topic=49496 | archive-date = 11 May 2011 | chapter-url = http://www.eoearth.org/article/Archaea?topic=49496 }}</ref>) It is hypothesized that the symbiosis originated when ancient archaea similar to modern [[Methanogenesis|methanogenic]] archaea, invaded and lived within bacteria similar to modern [[myxobacteria]], eventually forming the early nucleus. This theory is analogous to the accepted theory for the origin of eukaryotic mitochondria and [[chloroplast]]s, which are thought to have developed from a similar endosymbiotic relationship between proto-eukaryotes and aerobic bacteria.<ref name="Margulis">{{cite book | last= Margulis | first= Lynn | author-link= Lynn Margulis |name-list-style= vanc | year= 1981 | title= Symbiosis in Cell Evolution | pages= [https://archive.org/details/symbiosisincelle00marg/page/206 206–227] | publisher= W. H. Freeman and Company | location= San Francisco | isbn= 978-0-7167-1256-5 | url= https://archive.org/details/symbiosisincelle00marg/page/206 }}</ref> One possibility is that the nuclear membrane arose as a new membrane system following the origin of [[mitochondrion|mitochondria]] in an [[Archaea|archaebacterial]] host.<ref name="Martin">{{cite journal |vauthors=Martin W |title=Archaebacteria (Archaea) and the origin of the eukaryotic nucleus |journal=Curr Opin Microbiol |volume=8 |issue=6 |pages=630–7 |date=December 2005 |pmid=16242992 |doi=10.1016/j.mib.2005.10.004 |url=}}</ref> The nuclear membrane may have served to protect the genome from damaging [[reactive oxygen species]] produced by the protomitochondria.<ref>Bernstein, H., Bernstein, C. (2017). Sexual Communication in Archaea, the Precursor to Eukaryotic Meiosis. In: Witzany, G. (eds) Biocommunication of Archaea. Springer, Cham. https://doi.org/10.1007/978-3-319-65536-9_7</ref> The archaeal origin of the nucleus is supported by observations that archaea and eukarya have similar genes for certain proteins, including [[histone]]s. Observations that myxobacteria are motile, can form multicellular complexes, and possess [[kinase]]s and [[G protein]]s similar to eukarya, support a bacterial origin for the eukaryotic cell.<ref name="Lopez-Garcia">{{cite journal | vauthors = López-García P, Moreira D | title = Selective forces for the origin of the eukaryotic nucleus | journal = BioEssays | volume = 28 | issue = 5 | pages = 525–33 | date = May 2006 | pmid = 16615090 | doi = 10.1002/bies.20413 | department = Review }}</ref>

A second model proposes that proto-eukaryotic cells evolved from bacteria without an endosymbiotic stage. This model is based on the existence of modern [[Planctomycetota]] bacteria that possess a nuclear structure with primitive pores and other compartmentalized membrane structures.<ref name="Fuerst">{{cite journal | vauthors = Fuerst JA | title = Intracellular compartmentation in planctomycetes | journal = Annual Review of Microbiology | volume = 59 | pages = 299–328 | year = 2005 | pmid = 15910279 | doi = 10.1146/annurev.micro.59.030804.121258 | department = Review }}</ref>  A similar proposal states that a eukaryote-like cell, the [[Eukaryote#External phylogeny: relationship to Archaea and Bacteria|chronocyte]], evolved first and [[phagocytosed]] archaea and bacteria to generate the nucleus and the eukaryotic cell.<ref name="Hartman">{{cite journal | vauthors = Hartman H, Fedorov A | title = The origin of the eukaryotic cell: a genomic investigation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 3 | pages = 1420–5 | date = February 2002 | pmid = 11805300 | pmc = 122206 | doi = 10.1073/pnas.032658599 | department = Primary | bibcode = 2002PNAS...99.1420H | doi-access = free }}</ref>

The most controversial model, known as ''[[viral eukaryogenesis]]'', posits that the membrane-bound nucleus, along with other eukaryotic features, originated from the infection of a prokaryote by a virus. The suggestion is based on similarities between eukaryotes and viruses such as linear DNA strands, mRNA capping, and tight binding to proteins (analogizing histones to [[viral envelope]]s). One version of the proposal suggests that the nucleus evolved in concert with [[phagocytosis]] to form an early cellular "[[predator]]".<ref name="Bell">{{cite journal | vauthors = Bell PJ | title = Viral eukaryogenesis: was the ancestor of the nucleus a complex DNA virus? | journal = Journal of Molecular Evolution | volume = 53 | issue = 3 | pages = 251–6 | date = September 2001 | pmid = 11523012 | doi = 10.1007/s002390010215 | s2cid = 20542871 | department = Comment | bibcode = 2001JMolE..53..251L | doi-access = free }}</ref> Another variant proposes that eukaryotes originated from early archaea infected by [[poxvirus]]es, on the basis of observed similarity between the [[DNA polymerase]]s in modern poxviruses and eukaryotes.<ref name="Takemura">{{cite journal | vauthors = Takemura M | title = Poxviruses and the origin of the eukaryotic nucleus | journal = Journal of Molecular Evolution | volume = 52 | issue = 5 | pages = 419–25 | date = May 2001 | pmid = 11443345 | doi = 10.1007/s002390010171 | s2cid = 21200827 | department = Primary | bibcode = 2001JMolE..52..419T }}</ref><ref name="Villareal">{{cite journal | vauthors = Villarreal LP, DeFilippis VR | title = A hypothesis for DNA viruses as the origin of eukaryotic replication proteins | journal = Journal of Virology | volume = 74 | issue = 15 | pages = 7079–84 | date = August 2000 | pmid = 10888648 | pmc = 112226 | doi = 10.1128/JVI.74.15.7079-7084.2000 | department = Primary }}</ref> It has been suggested that the unresolved question of the [[evolution of sex]] could be related to the viral eukaryogenesis hypothesis.<ref name="Bell2">{{cite journal | vauthors = Bell PJ | title = Sex and the eukaryotic cell cycle is consistent with a viral ancestry for the eukaryotic nucleus | journal = Journal of Theoretical Biology | volume = 243 | issue = 1 | pages = 54–63 | date = November 2006 | pmid = 16846615 | doi = 10.1016/j.jtbi.2006.05.015 | bibcode = 2006JThBi.243...54B | department = Primary <!-- but secondary to the original eukaryogenesis hypothesis --> }}</ref>

A more recent proposal, the ''exomembrane hypothesis'', suggests that the nucleus instead originated from a single ancestral cell that evolved a second exterior cell membrane; the interior membrane enclosing the original cell then became the nuclear membrane and evolved increasingly elaborate pore structures for passage of internally synthesized cellular components such as ribosomal subunits.<ref name="deRoos">{{cite journal | vauthors = de Roos AD | title = The origin of the eukaryotic cell based on conservation of existing interfaces | journal = Artificial Life | volume = 12 | issue = 4 | pages = 513–23 | year = 2006 | pmid = 16953783 | doi = 10.1162/artl.2006.12.4.513 | s2cid = 5963228 | department = Primary }}</ref>

==History<!--'Cytoblast' redirects here-->==
[[File:Leeuwenhoek1719RedBloodCells.jpg|thumb|upright=1.5|Oldest known depiction of cells and their nuclei by [[Antonie van Leeuwenhoek]], 1719]]
[[Image:Flemming1882Tafel1Fig14.jpg|thumb|Drawing of a ''[[Chironomus]]'' [[salivary gland]] cell published by [[Walther Flemming]] in 1882. The nucleus contains [[polytene chromosome]]s.
]]
The nucleus was the first organelle to be discovered. What is most likely the oldest preserved drawing dates back to the early microscopist Antonie van Leeuwenhoek (1632–1723). He observed a "lumen", the nucleus, in the red blood cells of [[salmon]].<ref>{{cite book | vauthors = Van Leeuwenhoek A | title = Opera Omnia, seu Arcana Naturae ope exactissimorum Microscopiorum detecta, experimentis variis comprobata, Epistolis ad varios illustres viros J. Arnold et Delphis, A. Beman, Lugdinum Batavorum | trans-title  = The Works of, or arcana of nature by means of exactissimorum microscopes had been detected and confirmed by a variety of experiments, the Epistles to the various illustrious men of valor J. Arnold and Delphi, A. Beman, Lugdina York 1719-1730 | language = la }} Cited in {{cite book | vauthors = Gerlach D | title = Geschichte der Mikroskopie | publisher = [[Verlag Harri Deutsch]] | location = Frankfurt am Main, Germany | date = 2009 | isbn = 978-3-8171-1781-9 }}</ref> Unlike mammalian red blood cells, those of other vertebrates still contain nuclei.<ref>{{cite journal |doi=10.1007/BF01283036 |title=The cytomorphic system of anucleate non-mammalian erythrocytes |year=1982 |vauthors=Cohen WD |journal=Protoplasma |volume=113 |issue=1 |pages=23–32|bibcode=1982Prpls.113...23C |s2cid=41287948 }}</ref>

The nucleus was also described by [[Franz Bauer]] in 1804<ref name="Harris">{{cite book | vauthors = Harris H | title =The Birth of the Cell | year =1999 | publisher =Yale University Press | location =New Haven | isbn =978-0-300-07384-3 | url-access =registration | url =https://archive.org/details/birthofcell0000harr }}</ref> and in more detail in 1831 by Scottish [[botanist]] [[Robert Brown (Scottish botanist from Montrose)|Robert Brown]] in a talk at the [[Linnean Society of London]]. Brown was studying [[orchid]]s under the microscope when he observed an opaque area, which he called the "areola" or "nucleus", in the cells of the flower's outer layer.<ref name="Robert Brown">{{Cite journal |last=Brown |first=Robert |name-list-style=vanc |date=2015-04-02 |year= |editor-last=Bennett |editor-first=John Joseph |editor2-last=Brown |editor2-first=Robert |title=On the Organs and Mode of Fecundation of Orchidex and Asclepiadea |url=https://www.cambridge.org/core/product/identifier/CBO9781107775473A024/type/book_part |journal=Miscellaneous Botanical Works I |series=Cambridge Library Collection - Botany and Horticulture |location=Cambridge |publisher=Cambridge University Press |volume=1 |pages=511–514 |doi=10.1017/cbo9781107775473.017 |isbn=978-1-108-07681-4}}</ref> He did not suggest a potential function.

In 1838, [[Matthias Schleiden]] proposed that the nucleus plays a role in generating cells, thus he introduced the name "'''cytoblast'''<!--boldface per WP:R#PLA-->" ("cell builder"). He believed that he had observed new cells assembling around "cytoblasts". [[Franz Meyen]] was a strong opponent of this view, having already described cells multiplying by division and believing that many cells would have no nuclei. The idea that cells can be generated de novo, by the "cytoblast" or otherwise, contradicted work by [[Robert Remak]] (1852) and [[Rudolf Virchow]] (1855) who decisively propagated the new paradigm that cells are generated solely by cells ("{{lang|la|Omnis cellula e cellula}}"). The function of the nucleus remained unclear.<ref name="Cremer">{{cite book | last =Cremer| first =Thomas | name-list-style = vanc | title =Von der Zellenlehre zur Chromosomentheorie | year =1985 | publisher =Springer Verlag | location =Berlin, Heidelberg, New York, Tokyo | isbn = 978-3-540-13987-4}} Online Version [http://www.t-cremer.de/main_de/cremer/personen/info_T_Cremer.htm#book here]</ref>

Between 1877 and 1878, [[Oscar Hertwig]] published several studies on the [[fertilization]] of [[sea urchin]] eggs, showing that the nucleus of the [[sperm]] enters the [[oocyte]] and fuses with its nucleus. This was the first time it was suggested that an individual develops from a (single) nucleated cell. This was in contradiction to [[Ernst Haeckel]]'s theory that the complete [[phylogeny]] of a species would be repeated during embryonic development, including generation of the first nucleated cell from a "monerula", a structureless mass of primordial protoplasm ("[[Urschleim]]"). Therefore, the necessity of the sperm nucleus for fertilization was discussed for quite some time. However, Hertwig confirmed his observation in other animal groups, including [[amphibians]] and [[molluscs]]. [[Eduard Strasburger]] produced the same results for plants in 1884. This paved the way to assign the nucleus an important role in heredity. In 1873, [[August Weismann]] postulated the equivalence of the maternal and paternal germ ''cells'' for heredity. The function of the nucleus as carrier of genetic information became clear only later, after mitosis was discovered and the [[Mendelian inheritance|Mendelian rules]] were rediscovered at the beginning of the 20th century; the [[chromosome theory of heredity]] was therefore developed.<ref name ="Cremer"/>

== See also ==
* [[Computed Corpuscle Sectioning]]
* [[Nucleus (neuroanatomy)]]
* [[Nucleoid]]
* [[Nucleomorph]]

== References ==
{{Reflist}}

== Further reading ==
{{refbegin|30em}}
* {{cite journal | vauthors = Goldman RD, Gruenbaum Y, Moir RD, Shumaker DK, Spann TP | title = Nuclear lamins: building blocks of nuclear architecture | journal = Genes & Development | volume = 16 | issue = 5 | pages = 533–47 | date = March 2002 | pmid = 11877373 | doi = 10.1101/gad.960502 | doi-access = free }}
:A review article about nuclear lamins, explaining their structure and various roles
* {{cite journal | vauthors = Görlich D, Kutay U | title = Transport between the cell nucleus and the cytoplasm | journal = Annual Review of Cell and Developmental Biology | volume = 15 | pages = 607–60 | year = 1999 | pmid = 10611974 | doi = 10.1146/annurev.cellbio.15.1.607 }}
:A review article about nuclear transport, explains the principles of the mechanism, and the various transport pathways
* {{cite journal | vauthors = Lamond AI, Earnshaw WC | title = Structure and function in the nucleus | journal = Science | volume = 280 | issue = 5363 | pages = 547–53 | date = April 1998 | pmid = 9554838 | doi = 10.1126/science.280.5363.547 | url = http://azolla.fc.ul.pt/aulas/BiologiaCelular/docs/nucleo.pdf | citeseerx = 10.1.1.323.5543 }}
:A review article about the nucleus, explaining the structure of chromosomes within the organelle, and describing the nucleolus and other subnuclear bodies
* {{cite journal | vauthors = Pennisi E | title = Evolutionary biology. The birth of the nucleus | journal = Science | volume = 305 | issue = 5685 | pages = 766–8 | date = August 2004 | pmid = 15297641 | doi = 10.1126/science.305.5685.766 | s2cid = 83769250 }}
:A review article about the evolution of the nucleus, explaining a number of different theories
* {{cite book | vauthors = Pollard TD, Earnshaw WC | title = Cell Biology | publisher = Saunders | year = 2004 | location = Philadelphia | isbn = 978-0-7216-3360-2 }}
:A university level textbook focusing on cell biology. Contains information on nucleus structure and function, including nuclear transport, and subnuclear domains
{{refend}}

== External links ==
{{Commons category|Cell nucleus}}
{{refbegin}}
{{Library resources box
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* {{cite web | title = The Nucleus | url = http://www.mechanobio.info/topics/cellular-organization/go-0005634 | work = MBInfo }}
* {{cite web | title = Learn about the Cell Nucleus | work = cellnucleus.com | url = http://www.cellnucleus.com/education_main.htm }} Website covering structure and function of the nucleus from the Department of Oncology at the University of Alberta.
* {{cite web | vauthors = Bickmore W | url = http://npd.hgu.mrc.ac.uk/user/?page=compartment | title = The Nuclear Protein Database | publisher = Medical Research Council Human Genetics Unit }} Information on nuclear components.
* {{cite web | title = The Nucleus Collection | url = http://cellimages.ascb.org/cdm4/browse.php?CISOROOT=%2Fp4041coll6 | work = Image & Video Library | publisher = The American Society for Cell Biology | archive-url = https://web.archive.org/web/20061112023405/http://cellimages.ascb.org/cdm4/browse.php?CISOROOT=%2Fp4041coll6 | archive-date = 12 November 2006 }} contains peer-reviewed still images and video clips that illustrate the nucleus.
* {{cite web | title = Nuclear Envelope and Nuclear Import Section | url = http://cellimages.ascb.org/u/?%2Fp4041coll11%2C62 | work = Landmark Papers in Cell Biology | archive-url = https://web.archive.org/web/20061117175431/http://cellimages.ascb.org/u/?%2Fp4041coll11%2C62 | archive-date = 17 November 2006 | veditors = Gall JG, McIntosh JR }} contains digitized commentaries and links to seminal research papers on the nucleus. Published online in the [http://cellimages.ascb.org/ Image & Video Library] {{Webarchive|url=https://web.archive.org/web/20110610012208/http://cellimages.ascb.org/ |date=10 June 2011 }} of [http://www.ascb.org/ The American Society for Cell Biology]
* {{cite web | title = Cytoplasmic patterns generated by human antibodies | url = http://www.antibodypatterns.com/cytoplasmic.php | work = AntibodyPatterns.com | archive-url = https://web.archive.org/web/20070102032704/http://www.antibodypatterns.com/cytoplasmic.php | archive-date = 2 January 2007 }}
{{refend}}

{{organelles}}
{{Nucleus}}

{{Authority control}}

{{DEFAULTSORT:Cell Nucleus}}
[[Category:Cell nucleus| ]]
[[Category:Cell anatomy]]
[[Category:Organelles]]