Microprocessor complex subunit DGCR8: Difference between revisions

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{{Short description|Protein-coding gene in the species Homo sapiens}}

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{{Infobox_gene}}

The '''DGCR8''' microprocessor complex subunit DGCR8''' ''([[DiGeorge syndrome]] chromosomal'' [or ''critical''] ''region 8)'' is a [[protein]] that in humans is encoded by the ''{{gene|DGCR8''}} [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: DGCR8 DiGeorge syndrome critical region gene 8| url = https://www.ncbi.nlm.nih.gov/sites/entrezgene?Db=gene&Cmd=ShowDetailView&TermToSearch=54487| accessdateaccess-date = }}</ref> In other animals, particularly the common [[model organism]]s ''[[Drosophila melanogaster]]'' and ''[[Caenorhabditis elegans]]'', the protein is known as ''Pasha'' (partner of [[Drosha]]).<ref>{{cite journal | vauthors = Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ | title = Processing of primary microRNAs by the Microprocessor complex | journal = Nature | volume = 432 | issue = 7014 | pages = 231–5 | date = Nov 2004 | pmid = 15531879 | doi = 10.1038/nature03049 | bibcode = 2004Natur.432..231D | s2cid = 4425505 }}</ref> It is a required component of the [[RNA interference]] pathway.

== Function ==

The subunit DGCR8 is localized to the [[cell nucleus]] and is required for [[microRNA]] (miRNA) processing. It binds to the other subunit [[Drosha]], an [[RNase III]] [[enzyme]], to form the [[microprocessor complex]] that cleaves a [[primary transcript]] known as pri-miRNA to a characteristic [[stem-loop]] structure known as a pre-miRNA, which is then further processed to miRNA fragments by the enzyme [[Dicer]]. DGCR8 contains an [[RNA]]-binding ___domain and is thought to bind pri-miRNA to stabilize it for processing by Drosha.<ref>{{cite journal | vauthors = Yeom KH, Lee Y, Han J, Suh MR, Kim VN | title = Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing | journal = Nucleic Acids Research | volume = 34 | issue = 16 | pages = 4622–9 | year = 2006 | pmid = 16963499 | pmc = 1636349 | doi = 10.1093/nar/gkl458 }}</ref>

DGCR8 is also required for some types of DNA repair. Removal of UV-induced DNA [[Pyrimidine dimer|photoproducts]], during [[Nucleotide excision repair#Transcription coupled repair (TC-NER)|transcription coupled nucleotide excision repair (TC-NER)]], depends on JNK phosphorylation of DGCR8 on [[serine]] 153.<ref name=Calses>{{cite journal |vauthors=Calses PC, Dhillon KK, Tucker N, Chi Y, Huang JW, Kawasumi M, Nghiem P, Wang Y, Clurman BE, Jacquemont C, Gafken PR, Sugasawa K, Saijo M, Taniguchi T |title=DGCR8 Mediates Repair of UV-Induced DNA Damage Independently of RNA Processing |journal=Cell Rep |volume=19 |issue=1 |pages=162–174 |year=2017 |pmid=28380355 |doi=10.1016/j.celrep.2017.03.021 |pmc=5423785}}</ref> While DGCR8 is known to function in microRNA biogenesis, this activity is not required for DGCR8-dependent removal of UV-induced photoproducts.<ref name=Calses /> [[Nucleotide excision repair]] is also needed for repair of oxidative DNA damage due to [[hydrogen peroxide]] ({{chem|H₂O₂}}), and DGCR8 depleted cells are sensitive to {{chem|H₂O₂}}.<ref name=Calses />

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* {{cite journal | vauthors = Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S | title = Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing | journal = EMBO Reports | volume = 1 | issue = 3 | pages = 287–92 | date = Sep 2000 | pmid = 11256614 | pmc = 1083732 | doi = 10.1093/embo-reports/kvd058 }}

* {{cite journal | vauthors = Shiohama A, Sasaki T, Noda S, Minoshima S, Shimizu N | title = Molecular cloning and expression analysis of a novel gene DGCR8 located in the DiGeorge syndrome chromosomal region | journal = Biochemical and Biophysical Research Communications | volume = 304 | issue = 1 | pages = 184–90 | date = Apr 2003 | pmid = 12705904 | doi = 10.1016/S0006-291X(03)00554-0 }}

* {{cite journal | vauthors = Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R | title = The Microprocessor complex mediates the genesis of microRNAs | journal = Nature | volume = 432 | issue = 7014 | pages = 235–40 | date = Nov 2004 | pmid = 15531877 | doi = 10.1038/nature03120 | bibcode = 2004Natur.432..235G | s2cid = 4389261 }}

* {{cite journal | vauthors = Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN | title = The Drosha-DGCR8 complex in primary microRNA processing | journal = Genes & Development | volume = 18 | issue = 24 | pages = 3016–27 | date = Dec 2004 | pmid = 15574589 | pmc = 535913 | doi = 10.1101/gad.1262504 }}

* {{cite journal | vauthors = Landthaler M, Yalcin A, Tuschl T | title = The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis | journal = Current Biology | volume = 14 | issue = 23 | pages = 2162–7 | date = Dec 2004 | pmid = 15589161 | doi = 10.1016/j.cub.2004.11.001 | bibcode = 2004CBio...14.2162L | hdl = 11858/00-001M-0000-0012-EB83-3 | s2cid = 13266269 | hdl-access = free }}

* {{cite journal | vauthors = Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK, Sohn SY, Cho Y, Zhang BT, Kim VN | title = Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex | journal = Cell | volume = 125 | issue = 5 | pages = 887–901 | date = Jun 2006 | pmid = 16751099 | doi = 10.1016/j.cell.2006.03.043 | doi-access = free }}

* {{cite journal | vauthors = Faller M, Matsunaga M, Yin S, Loo JA, Guo F | title = Heme is involved in microRNA processing | journal = Nature Structural & Molecular Biology | volume = 14 | issue = 1 | pages = 23–9 | date = Jan 2007 | pmid = 17159994 | doi = 10.1038/nsmb1182 | s2cid = 17463646 }}

* {{cite journal | vauthors = Sohn SY, Bae WJ, Kim JJ, Yeom KH, Kim VN, Cho Y | title = Crystal structure of human DGCR8 core | journal = Nature Structural & Molecular Biology | volume = 14 | issue = 9 | pages = 847–53 | date = Sep 2007 | pmid = 17704815 | doi = 10.1038/nsmb1294 | s2cid = 18561478 }}

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