Biology:Microprocessor complex subunit DGCR8
 Generic protein structure example |
The microprocessor complex subunit DGCR8 (DiGeorge syndrome critical region 8) is a protein that in humans is encoded by the DGCR8 gene.[1] In other animals, particularly the common model organisms Drosophila melanogaster and Caenorhabditis elegans, the protein is known as Pasha (partner of Drosha).[2] 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.[3]
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.[4] While DGCR8 is known to function in microRNA biogenesis, this activity is not required for DGCR8-dependent removal of UV-induced photoproducts.[4] 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.[4]
References
- ↑ "Entrez Gene: DGCR8 DiGeorge syndrome critical region gene 8". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=54487.
- ↑ "Processing of primary microRNAs by the Microprocessor complex". Nature 432 (7014): 231–5. Nov 2004. doi:10.1038/nature03049. PMID 15531879. Bibcode: 2004Natur.432..231D.
- ↑ "Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing". Nucleic Acids Research 34 (16): 4622–9. 2006. doi:10.1093/nar/gkl458. PMID 16963499.
- ↑ 4.0 4.1 4.2 "DGCR8 Mediates Repair of UV-Induced DNA Damage Independently of RNA Processing". Cell Rep 19 (1): 162–174. 2017. doi:10.1016/j.celrep.2017.03.021. PMID 28380355.
Further reading
- "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports 1 (3): 287–92. Sep 2000. doi:10.1093/embo-reports/kvd058. PMID 11256614.
- "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. Apr 2003. doi:10.1016/S0006-291X(03)00554-0. PMID 12705904.
- "The Microprocessor complex mediates the genesis of microRNAs". Nature 432 (7014): 235–40. Nov 2004. doi:10.1038/nature03120. PMID 15531877. Bibcode: 2004Natur.432..235G.
- "The Drosha-DGCR8 complex in primary microRNA processing". Genes & Development 18 (24): 3016–27. Dec 2004. doi:10.1101/gad.1262504. PMID 15574589.
- "The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis". Current Biology 14 (23): 2162–7. Dec 2004. doi:10.1016/j.cub.2004.11.001. PMID 15589161.
- "Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex". Cell 125 (5): 887–901. Jun 2006. doi:10.1016/j.cell.2006.03.043. PMID 16751099.
- "Heme is involved in microRNA processing". Nature Structural & Molecular Biology 14 (1): 23–9. Jan 2007. doi:10.1038/nsmb1182. PMID 17159994.
- "Crystal structure of human DGCR8 core". Nature Structural & Molecular Biology 14 (9): 847–53. Sep 2007. doi:10.1038/nsmb1294. PMID 17704815.
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