Figure 1.
RNAi-based gene silencing pathways in H sapiens. (a) Dicer cleaves long double-stranded RNA (dsRNA) or short-hairpin RNA (shRNA) into functional siRNA with characteristic 3′ overhangs. siRNAs are incorporated into RISC, recognize the target mRNA through an unknown subunit(s), and cleavage is performed by AGO2. (b) Precursor microRNAs (pre-miRNA), which themselves are a cleavage product of a primary microRNA transcript, are further processed by Dicer into functional miRNAs that associate with AGO2 into a miRNA ribonucleoprotein (miRNP). miRNPs recognize their target mRNAs resulting in translation inhibition by an undefined mechanism. (c) Transcriptional gene silencing is initiated by Dicer-mediated cleavage of long dsRNA (eg, centromere dsRNA) into siRNA that associate with the RITS complex. Putative components of H sapiens RITS are depicted: AGO-argonaute; DNMT-DNA methyltransferase; HDAC-histone deacetylase; HP1-heterochromatin protein 1.