Microprocessor complex subunit DGCR8 explained

The microprocessor complex subunit DGCR8 (DiGeorge syndrome critical region 8) is a protein that in humans is encoded by the 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. Nucleotide excision repair is also needed for repair of oxidative DNA damage due to hydrogen peroxide, and DGCR8 depleted cells are sensitive to .

Further reading

• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S . Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing . EMBO Reports . 1 . 3 . 287–92 . Sep 2000 . 11256614 . 1083732 . 10.1093/embo-reports/kvd058 .
• Shiohama A, Sasaki T, Noda S, Minoshima S, Shimizu N . 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 . 12705904 . 10.1016/S0006-291X(03)00554-0 .
• Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R . The Microprocessor complex mediates the genesis of microRNAs . Nature . 432 . 7014 . 235–40 . Nov 2004 . 15531877 . 10.1038/nature03120 . 2004Natur.432..235G . 4389261 .
• Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN . The Drosha-DGCR8 complex in primary microRNA processing . Genes & Development . 18 . 24 . 3016–27 . Dec 2004 . 15574589 . 535913 . 10.1101/gad.1262504 .
• Landthaler M, Yalcin A, Tuschl T . 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 . 15589161 . 10.1016/j.cub.2004.11.001 . 2004CBio...14.2162L . 11858/00-001M-0000-0012-EB83-3 . 13266269 . free .
• Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK, Sohn SY, Cho Y, Zhang BT, Kim VN . Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex . Cell . 125 . 5 . 887–901 . Jun 2006 . 16751099 . 10.1016/j.cell.2006.03.043 . free .
• Faller M, Matsunaga M, Yin S, Loo JA, Guo F . Heme is involved in microRNA processing . Nature Structural & Molecular Biology . 14 . 1 . 23–9 . Jan 2007 . 17159994 . 10.1038/nsmb1182 . 17463646 .
• Sohn SY, Bae WJ, Kim JJ, Yeom KH, Kim VN, Cho Y . Crystal structure of human DGCR8 core . Nature Structural & Molecular Biology . 14 . 9 . 847–53 . Sep 2007 . 17704815 . 10.1038/nsmb1294 . 18561478 .

Notes and References

1. Web site: Entrez Gene: DGCR8 DiGeorge syndrome critical region gene 8.
2. Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ . Processing of primary microRNAs by the Microprocessor complex . Nature . 432 . 7014 . 231–5 . Nov 2004 . 15531879 . 10.1038/nature03049 . 2004Natur.432..231D . 4425505 .
3. Yeom KH, Lee Y, Han J, Suh MR, Kim VN . Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing . Nucleic Acids Research . 34 . 16 . 4622–9 . 2006 . 16963499 . 1636349 . 10.1093/nar/gkl458 .
4. 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 . DGCR8 Mediates Repair of UV-Induced DNA Damage Independently of RNA Processing . Cell Rep . 19 . 1 . 162–174 . 2017 . 28380355 . 10.1016/j.celrep.2017.03.021 . 5423785.