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RNA-induced silencing complex (RISC)

May be same as trimeric miRLC Function: - RNA cleavage & translational silencing - inhibits translation of mRNA. - recruited by siRNA - the RISC loading complex loads miRNA onto AGO2 - the 'minimal RISC' appears to include AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA) - these guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing - the precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA & its target - binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by AGO2 - binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, & this is independent of endonuclease activity - may inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E - may also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit & prevents its association with the 40S ribosomal subunit - inhibition of translational initiation leads to accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur - RISC-mediated translational repression may also be observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR) Structure: - subunits: AGO2, DICER1 & TARBP2 - AGO2 bound to the mature miRNA constitutes the minimal RISC & may subsequently dissociate from DICER1 & TARBP2

Related

messenger RNA RISC complex (GO:0016442) RISC loading complex; micro-RNA loading complex (miRLC) short interfering double-stranded RNA; antisense oligonucleotide (siRNA, microRNA, miRNA)

General

molecular complex

Properties

COMPARTMENT: cell nucleus

References

  1. Mendell JT. MicroRNAs: Critical Regulators of Development, Cellular Physiology and Malignancy. Cell Cycle. 2005 Sep 15;4(9) [Epub ahead of print] PMID: 16096373
  2. UniProt :accession Q9NX0