RNA interference machinery (RNAi machinery)

RNA interference (RNAi) machinery is the conserved cellular system that uses small noncoding RNAs—principally siRNAs and miRNAs—to direct the RNA-induced silencing complex (RISC) to complementary mRNAs, resulting in sequence-specific gene silencing by mRNA cleavage, deadenylation/decay, or translational repression[2][5]. Key components include the RNase III enzyme Dicer, which processes dsRNA or pre-miRNA into ~21–25 nt small RNAs with characteristic 3′ overhangs, and Argonaute proteins (notably AGO2) that bind the guide strand and mediate target recognition and cleavage within RISC[3][5][6]. The pathway regulates endogenous gene expression, contributes to development and genome stability, and provides defense against exogenous nucleic acids and transposons; it is widely leveraged by siRNA/shRNA/miRNA therapeutics to silence disease-driving genes[1][5][6][9].

Other names

RNA interference pathway[2]RNA silencing pathway[2]RNA-induced silencing complex pathway (RISC pathway)[5]Small RNA pathway (siRNA/miRNA pathway)[1][6]Post-transcriptional gene silencing machinery (PTGS)[3]

Dicer processes double-stranded RNA (dsRNA, including siRNA precursors or pre-miRNA) into ~20–25 nt small RNAs with 2-nt 3′ overhangs[3][6]. Guide strand loading into Argonaute to form RISC; Argonaute (Ago2) provides endonucleolytic “slicer” activity[5][6]. siRNA: sequence-perfect or near-perfect pairing → target mRNA cleavage and degradation[1][6]. miRNA: partial complementarity → translational repression and/or mRNA deadenylation/decay; in mammals, reduced mRNA levels account for most decreased protein output[1][7]. Pathway roles include defense against viruses/exogenous nucleic acids and transposon silencing; regulation of endogenous genes[5][6][9].