Microprocessor complex
The Microprocessor complex is a protein complex involved in the processing of microRNA (miRNA).[1][2] It consists minimally of two proteins: Drosha, a ribonuclease III enzyme; and DGCR8 (also known as Pasha), a double-stranded RNA binding protein. Located in the cell nucleus, the complex cleaves primary miRNA (pri-miRNA), typically at least 1000 nucleotides long and derived from either transcripts of their own genes or from introns, into precursor miRNA (pre-miRNA) molecules of around 70 nucleotides containing a stem-loop or hairpin structure. DCGR8 recognizes the junctions between hairpin structures and single-stranded RNA and serves to orient Drosha to cleave around 11 nucleotides away from the junctions. In addition to the minimal catalytically active Microprocessor components, additional cofactors such as DEAD box RNA helicases and heterogeneous nuclear ribonucleoproteins may be present in the complex to mediate the activity of Drosha. Microprocessor cleavage of pri-miRNAs typically occurs co-transcriptionally and leaves a characteristic RNase III single-stranded overhang of 2-3 nucleotides, which serves as a recognition element for the transport protein exportin-5. Pre-miRNAs are exported from the nucleus to the cytoplasm in a RanGTP-dependent manner and are further processed, typically by the endoribonuclease enzyme Dicer.[3][4][5] The processing pathways that occur in the cytoplasm are largely identical for microRNA and for small interfering RNA involved in RNA interference.[3]
References
- ^ Gregory, RI; Yan, KP; Amuthan, G; Chendrimada, T; Doratotaj, B; Cooch, N; Shiekhattar, R (11 November 2004). "The Microprocessor complex mediates the genesis of microRNAs". Nature. 432 (7014): 235–40. PMID 15531877.
- ^ Denli, AM; Tops, BB; Plasterk, RH; Ketting, RF; Hannon, GJ (11 November 2004). "Processing of primary microRNAs by the Microprocessor complex". Nature. 432 (7014): 231–5. PMID 15531879.
- ^ a b Wilson, RC; Doudna, JA (2013). "Molecular mechanisms of RNA interference". Annual review of biophysics. 42: 217–39. PMID 23654304.
- ^ Siomi, H; Siomi, MC (14 May 2010). "Posttranscriptional regulation of microRNA biogenesis in animals". Molecular cell. 38 (3): 323–32. PMID 20471939.
- ^ Macias, S; Cordiner, RA; Cáceres, JF (August 2013). "Cellular functions of the microprocessor". Biochemical Society transactions. 41 (4): 838–43. PMID 23863141.