Editing Cell nucleus (section)

== 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>
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