Editing Cell nucleus (section)

==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" />