Microprocessor complex subunit DGCR8

Definition:

Component of the microprocessor complex that acts as a RNA- and heme-binding protein that is involved in the initial step of microRNA (miRNA) biogenesis. Component of the microprocessor complex that is required to process primary miRNA transcripts (pri-miRNAs) to release precursor miRNA (pre-miRNA) in the nucleus. Within the microprocessor complex, DGCR8 function as a molecular anchor necessary for the recognition of pri-miRNA at dsRNA-ssRNA junction and directs DROSHA to cleave 11 bp away form the junction to release hairpin-shaped pre-miRNAs that are subsequently cut by the cytoplasmic DICER to generate mature miRNAs. The heme-bound DGCR8 dimer binds pri-miRNAs as a cooperative trimer (of dimers) and is active in triggering pri-miRNA cleavage, whereas the heme-free DGCR8 monomer binds pri-miRNAs as a dimer and is much less active. Both double-stranded and single-stranded regions of a pri-miRNA are required for its binding. Specifically recognizes and binds N6-methyladenosine (m6A)-containing pri-miRNAs, a modification required for pri-miRNAs processing. Involved in the silencing of embryonic stem cell self-renewal (By similarity).

References:

[1]. S Chul Kwon, et al. Structure of Human DROSHA. Cell. 2016 Jan 14;164(1-2):81-90. [Content Brief]

[2]. Tuan Anh Nguyen, et al. Functional Anatomy of the Human Microprocessor. Cell. 2015 Jun 4;161(6):1374-87. [Content Brief]

[3]. Michael Faller, et al. Heme is involved in microRNA processing. Nat Struct Mol Biol. 2007 Jan;14(1):23-9. [Content Brief]

[4]. Jinju Han, et al. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 2004 Dec 15;18(24):3016-27. [Content Brief]

[5]. Kaleb M Pauley, et al. Formation of GW bodies is a consequence of microRNA genesis. EMBO Rep. 2006 Sep;7(9):904-10. [Content Brief]

[6]. Claudio R Alarcón, et al. N6-methyladenosine marks primary microRNAs for processing. Nature. 2015 Mar 26;519(7544):482-5. [Content Brief]

[7]. Richard I Gregory, et al. The Microprocessor complex mediates the genesis of microRNAs. Nature. 2004 Nov 11;432(7014):235-40. [Content Brief]

[8]. Jinju Han, et al. Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex. Cell. 2006 Jun 2;125(5):887-901. [Content Brief]

[9]. Kyu-Hyeon Yeom, et al. Characterization of DGCR8/Pasha, the essential cofactor for Drosha in primary miRNA processing. Nucleic Acids Res. 2006;34(16):4622-9. [Content Brief]

[10]. Markus Landthaler, et al. The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis. Curr Biol. 2004 Dec 14;14(23):2162-7. [Content Brief]

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