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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'''DGCR8''' (DiGeorge syndrome chromosomal region 8) is a [[protein]] that in humans is encoded by the ''DGCR8'' [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: DGCR8 DiGeorge syndrome critical region gene 8| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=54487| accessdate = }}</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|last1=Denli|first1=AM|last2=Tops|first2=BB|last3=Plasterk|first3=RH|last4=Ketting|first4=RF|last5=Hannon|first5=GJ|title=Processing of primary microRNAs by the Microprocessor complex.|journal=Nature|date=11 November 2004|volume=432|issue=7014|pages=231-5|pmid=15531879}}</ref> It is a required component of the [[RNA interference]] pathway.

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The ''' microprocessor complex subunit DGCR8''' ''([[DiGeorge syndrome]] chromosomalcritical 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 = httphttps://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 |last1 vauthors = Denli|first1= AM|last2=, Tops|first2= BB|last3=, Plasterk|first3= RH|last4=, Ketting|first4= RF|last5=, Hannon|first5= GJ | title = Processing of primary microRNAs by the Microprocessor complex. | journal = Nature|date=11 November 2004| volume = 432 | issue = 7014 | pages =231-5 231–5 | 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 protein is localized to the [[cell nucleus]] and is required for [[microRNA]] (miRNA) processing. It binds to [[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]]. Pasha contains an [[RNA]]-binding ___domain and is thought to bind pri-miRNA to stabilize it for processing by Drosha.<ref>{{cite journal | pmid=16963499 | year=2006 | last1=Yeom | first1=KH | last2=Lee | first2=Y | last3=Han | first3=J | last4=Suh | first4=MR | last5=Kim | first5=VN | title=Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing | volume=34 | issue=16 | pages=4622–9 | doi=10.1093/nar/gkl458 | pmc=1636349 | journal=Nucleic acids research}}</ref>

The proteinsubunit 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[[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]]. PashaDGCR8 contains an [[RNA]]-binding ___domain and is thought to bind pri-miRNA to stabilize it for processing by Drosha.<ref>{{cite journal | pmid=16963499vauthors | year=2006 | last1=Yeom | first1=KH, | last2=Lee | first2=Y, | last3=Han | first3=J, | last4=Suh | first4=MR, | last5=Kim | first5=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 | doiyear =10.1093/nar/gkl458 2006 | pmid = 16963499 | pmc = 1636349 | journaldoi =Nucleic acids10.1093/nar/gkl458 research}}</ref>

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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 />

==References==

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==Further readingReferences ==

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== Further reading ==

{{refbegin | 2}}

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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 }}

| citations =

* {{cite journal | authorvauthors =Maruyama KShiohama A, SuganoSasaki T, Noda S, Minoshima S, Shimizu N | title =Oligo-capping: aMolecular simplecloning methodand toexpression replaceanalysis theof capa structurenovel ofgene eukaryoticDGCR8 mRNAslocated within oligoribonucleotides.the DiGeorge syndrome chromosomal region | journal =Gene Biochemical and Biophysical Research Communications | volume =138 304 | issue = 1-2 | pages = 171–4184–90 |year date = 1994Apr 2003 | pmid = 812529812705904 | doi = 10.1016/0378S0006-1119291X(9403)9080200554-8 0 }}

* {{cite journal | authorvauthors =Suzuki YGregory RI, Yoshitomo-NakagawaYan KKP, MaruyamaAmuthan KG, ''etChendrimada al.''T, |title=ConstructionDoratotaj andB, characterizationCooch ofN, aShiekhattar fullR length-enriched| andtitle a= 5'-end-enrichedThe cDNAMicroprocessor library.complex mediates the genesis of microRNAs | journal =Gene Nature | volume =200 432 | issue = 1-27014 | pages = 149–56235–40 |year date = 1997Nov 2004 | pmid = 937314915531877 | doi = 10.10161038/S0378-1119(97)00411-3nature03120 | bibcode = 2004Natur.432..235G | s2cid = 4389261 }}

* {{cite journal | authorvauthors =Hartley JLHan J, Lee Y, Yeom KH, Kim YK, TempleJin GFH, BraschKim MAVN | title =DNA cloningThe usingDrosha-DGCR8 complex in vitroprimary site-specificmicroRNA recombination.processing | journal =Genome Res.Genes & Development | volume =10 18 | issue = 1124 | pages = 1788–953016–27 |year date = 2001Dec 2004 | pmid = 1107686315574589 |doi pmc =10.1101/gr.143000 535913 | pmcdoi =310948 10.1101/gad.1262504 }}

* {{cite journal | authorvauthors =Simpson JC, WellenreutherLandthaler RM, PoustkaYalcin A, ''etTuschl al.''T | title =Systematic subcellularThe localizationhuman ofDiGeorge novelsyndrome proteinscritical identifiedregion bygene large-scale8 cDNAand sequencingIts D. melanogaster homolog are required for miRNA biogenesis | journal =EMBO Rep.Current Biology | volume =1 14 | issue = 323 | pages = 287–922162–7 |year date = 2001Dec 2004 | pmid = 1125661415589161 | doi = 10.10931016/embo-reportsj.cub.2004.11.001 | bibcode = 2004CBio...14.2162L | hdl = 11858/kvd05800-001M-0000-0012-EB83-3 | s2cid = 13266269 | pmchdl-access =1083732 free }}

* {{cite journal | authorvauthors =Strausberg RLHan J, FeingoldLee EAY, GrouseYeom LHKH, ''etNam al.''JW, |title=GenerationHeo andI, initialRhee analysisJK, ofSohn moreSY, thanCho 15Y,000 full-lengthZhang humanBT, andKim mouseVN cDNA| sequences.title |journal=Proc. Natl.Molecular Acad.basis Sci.for U.S.A.the recognition of primary microRNAs by the Drosha-DGCR8 complex | journal = Cell | volume =99 125 | issue = 265 | pages = 16899–903887–901 |year date = 2003Jun 2006 | pmid = 1247793216751099 | doi = 10.10731016/pnasj.242603899 cell.2006.03.043 | pmcdoi-access =139241 free }}

* {{cite journal | authorvauthors =Shiohama AFaller M, SasakiMatsunaga TM, NodaYin S, ''etLoo al.''JA, Guo F | title =Molecular cloningHeme andis expressioninvolved analysisin ofmicroRNA aprocessing novel| genejournal DGCR8= locatedNature inStructural the& DiGeorgeMolecular syndromeBiology chromosomal| region.volume |journal=Biochem. Biophys. Res. Commun.14 |volume=304 |issue = 1 | pages = 184–9023–9 |year date = 2003Jan 2007 | pmid = 1270590417159994 | doi = 10.10161038/S0006-291X(03)00554-0nsmb1182 | s2cid = 17463646 }}

* {{cite journal | authorvauthors =Ota TSohn SY, SuzukiBae YWJ, NishikawaKim TJJ, ''etYeom al.''KH, Kim VN, Cho Y | title =Complete sequencingCrystal and characterizationstructure of 21,243 full-length human cDNAs.DGCR8 core | journal =Nat. Genet.Nature Structural & Molecular Biology | volume =36 14 | issue = 19 | pages = 40–5847–53 |year date = 2004Sep 2007 | pmid = 1470203917704815 | doi = 10.1038/ng1285nsmb1294 | s2cid = 18561478 }}

*{{cite journal | author=Collins JE, Wright CL, Edwards CA, ''et al.'' |title=A genome annotation-driven approach to cloning the human ORFeome. |journal=Genome Biol. |volume=5 |issue= 10 |pages= R84 |year= 2005 |pmid= 15461802 |doi= 10.1186/gb-2004-5-10-r84 | pmc=545604 }}

*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 }}

*{{cite journal | author=Wiemann S, Arlt D, Huber W, ''et al.'' |title=From ORFeome to biology: a functional genomics pipeline. |journal=Genome Res. |volume=14 |issue= 10B |pages= 2136–44 |year= 2004 |pmid= 15489336 |doi= 10.1101/gr.2576704 | pmc=528930 }}

*{{cite journal | author=Gregory RI, Yan KP, Amuthan G, ''et al.'' |title=The Microprocessor complex mediates the genesis of microRNAs. |journal=Nature |volume=432 |issue= 7014 |pages= 235–40 |year= 2004 |pmid= 15531877 |doi= 10.1038/nature03120 }}

*{{cite journal | author=Han J, Lee Y, Yeom KH, ''et al.'' |title=The Drosha-DGCR8 complex in primary microRNA processing. |journal=Genes Dev. |volume=18 |issue= 24 |pages= 3016–27 |year= 2005 |pmid= 15574589 |doi= 10.1101/gad.1262504 | pmc=535913 }}

*{{cite journal | author=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=Curr. Biol. |volume=14 |issue= 23 |pages= 2162–7 |year= 2005 |pmid= 15589161 |doi= 10.1016/j.cub.2004.11.001 }}

*{{cite journal | author=Mehrle A, Rosenfelder H, Schupp I, ''et al.'' |title=The LIFEdb database in 2006. |journal=Nucleic Acids Res. |volume=34 |issue= Database issue |pages= D415–8 |year= 2006 |pmid= 16381901 |doi= 10.1093/nar/gkj139 | pmc=1347501 }}

*{{cite journal | author=Han J, Lee Y, Yeom KH, ''et al.'' |title=Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. |journal=Cell |volume=125 |issue= 5 |pages= 887–901 |year= 2006 |pmid= 16751099 |doi= 10.1016/j.cell.2006.03.043 }}

*{{cite journal | author=Faller M, Matsunaga M, Yin S, ''et al.'' |title=Heme is involved in microRNA processing. |journal=Nat. Struct. Mol. Biol. |volume=14 |issue= 1 |pages= 23–9 |year= 2007 |pmid= 17159994 |doi= 10.1038/nsmb1182 }}

*{{cite journal | author=Sohn SY, Bae WJ, Kim JJ, ''et al.'' |title=Crystal structure of human DGCR8 core. |journal=Nat. Struct. Mol. Biol. |volume=14 |issue= 9 |pages= 847–53 |year= 2007 |pmid= 17704815 |doi= 10.1038/nsmb1294 }}

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{{PDB Gallery|geneid=54487}}

[[Category:MicroRNA]]

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[[Category:ProteinsRNA interference]]

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[[Category:DNA repair]]

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[[Category:Proteins]]

[[Category:MicroRNA]]