RNA-induced silencing complex (RISC)

Introduction

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

More general terms

• molecular complex

Additional terms

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