DGCR8

The DGCR8 microprocessor complex subunit (DiGeorge syndrome chromosomal [or critical] region 8) is a protein that in humans is encoded by the DGCR8 gene.[4] In other animals, particularly the common model organisms Drosophila melanogaster and Caenorhabditis elegans, the protein is known as Pasha (partner of Drosha).[5] It is a required component of the RNA interference pathway.

DGCR8
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1X47, 2YT4, 3LE4, 5B16
Identifiers
Aliases	DGCR8, C22orf12, DGCRK6, Gy1, pasha, Pasha, DGCR8 microprocessor complex subunit, microprocessor complex subunit
External IDs	OMIM: 609030 MGI: 2151114 HomoloGene: 11223 GeneCards: DGCR8
Gene location (Human) Chr. Chromosome 22 (human)[1] Band 22q11.21 Start 20,080,232 bp[1] End 20,111,877 bp[1]
RNA expression pattern More reference expression data
Gene ontology Molecular function • primary miRNA binding • ribonuclease III activity • double-stranded RNA binding • GO:0001948 protein binding • heme binding • protein homodimerization activity • metal ion binding • RNA binding • identical protein binding Cellular component • cytoplasm • microprocessor complex • nucleolus • cell nucleus • nucleoplasm • GO:0097483, GO:0097481 postsynaptic density Biological process • regulation of stem cell proliferation • primary miRNA processing • RNA phosphodiester bond hydrolysis, endonucleolytic • RNA phosphodiester bond hydrolysis • miRNA metabolic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	54487	94223
Ensembl	ENSG00000128191	n/a
UniProt	Q8WYQ5	Q9EQM6
RefSeq (mRNA)	NM_001190326 NM_022720	NM_033324
RefSeq (protein)	NP_001177255 NP_073557	NP_201581
Location (UCSC)	Chr 22: 20.08 – 20.11 Mb	n/a
PubMed search	[2]	[3]
Wikidata
View/Edit Human View/Edit Mouse

Function

DGCR8 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. DGCR8 contains an RNA-binding domain and is thought to bind pri-miRNA to stabilize it for processing by Drosha.[6]

DGCR8 is also required for some types of DNA repair. Removal of UV-induced DNA photoproducts, during transcription coupled nucleotide excision repair (TC-NER), depends on JNK phosphorylation of DGCR8 on serine 153.[7] While DGCR8 is known to function in microRNA biogenesis, this activity is not required for DGCR8-dependent removal of UV-induced photoproducts.[7] Nucleotide excision repair is also needed for repair of oxidative DNA damage due to hydrogen peroxide (H₂O₂), and DGCR8 depleted cells are sensitive to H₂O₂.[7]

References

1. GRCh38: Ensembl release 89: ENSG00000128191 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Entrez Gene: DGCR8 DiGeorge syndrome critical region gene 8".
5. Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ (Nov 2004). "Processing of primary microRNAs by the Microprocessor complex". Nature. 432 (7014): 231–5. doi:10.1038/nature03049. PMID 15531879.
6. Yeom KH, Lee Y, Han J, Suh MR, Kim VN (2006). "Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing". Nucleic Acids Research. 34 (16): 4622–9. doi:10.1093/nar/gkl458. PMC 1636349. PMID 16963499.
7. 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 (2017). "DGCR8 Mediates Repair of UV-Induced DNA Damage Independently of RNA Processing". Cell Rep. 19 (1): 162–174. doi:10.1016/j.celrep.2017.03.021. PMC 5423785. PMID 28380355.

Further reading

• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (Sep 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
• Shiohama A, Sasaki T, Noda S, Minoshima S, Shimizu N (Apr 2003). "Molecular cloning and expression analysis of a novel gene DGCR8 located in the DiGeorge syndrome chromosomal region". Biochemical and Biophysical Research Communications. 304 (1): 184–90. doi:10.1016/S0006-291X(03)00554-0. PMID 12705904.
• Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R (Nov 2004). "The Microprocessor complex mediates the genesis of microRNAs". Nature. 432 (7014): 235–40. doi:10.1038/nature03120. PMID 15531877.
• Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN (Dec 2004). "The Drosha-DGCR8 complex in primary microRNA processing". Genes & Development. 18 (24): 3016–27. doi:10.1101/gad.1262504. PMC 535913. PMID 15574589.
• Landthaler M, Yalcin A, Tuschl T (Dec 2004). "The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis". Current Biology. 14 (23): 2162–7. doi:10.1016/j.cub.2004.11.001. hdl:11858/00-001M-0000-0012-EB83-3. PMID 15589161.
• Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK, Sohn SY, Cho Y, Zhang BT, Kim VN (Jun 2006). "Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex". Cell. 125 (5): 887–901. doi:10.1016/j.cell.2006.03.043. PMID 16751099.
• Faller M, Matsunaga M, Yin S, Loo JA, Guo F (Jan 2007). "Heme is involved in microRNA processing". Nature Structural & Molecular Biology. 14 (1): 23–9. doi:10.1038/nsmb1182. PMID 17159994.
• Sohn SY, Bae WJ, Kim JJ, Yeom KH, Kim VN, Cho Y (Sep 2007). "Crystal structure of human DGCR8 core". Nature Structural & Molecular Biology. 14 (9): 847–53. doi:10.1038/nsmb1294. PMID 17704815.