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. 2003 Dec;67(4):657–685. doi: 10.1128/MMBR.67.4.657-685.2003

FIG. 2.

FIG. 2.

FIG. 2.

FIG. 2.

Two-step model for the mechanism of gene silencing induced by double-stranded RNA. In step I, dsRNA is cleaved by the Dicer enzyme to produce siRNAs. A putative kinase seems to maintain 5′ phosphorylation at this step. The siRNAs have also been proposed to be responsible for nuclear DNA methylation (•) and systemic spread of silencing. Amplification might occur due to the presence of RdRP (▴). In step II, the siRNAs generated in step I bind to the nuclease complex (RISC). A helicase present in the complex might activate RISC by unwinding the siRNAs. The antisense component of siRNA in the RISC guides the complex towards the cognate mRNA (), resulting in endonucleolytic cleavage () of the mRNA. RdDM, RNA-dependent DNA methylation.