Microprocessor complex subunit DGCR8

The microprocessor complex subunit DGCR8 (DiGeorge syndrome 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
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesDGCR8, C22orf12, DGCRK6, Gy1, pasha, Pasha, DGCR8 microprocessor complex subunit, microprocessor complex subunit
External IDsOMIM: 609030; MGI: 2151114; HomoloGene: 11223; GeneCards: DGCR8; OMA:DGCR8 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001190326
NM_022720

NM_033324

RefSeq (protein)

NP_001177255
NP_073557

NP_201581

Location (UCSC)Chr 22: 20.08 – 20.11 Mbn/a
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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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.[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

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000128191Ensembl, 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. Bibcode:2004Natur.432..231D. doi:10.1038/nature03049. PMID 15531879. S2CID 4425505.
  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. ^ a b c 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

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