Fig 2.

RNA Interference. Upon cellular entry, exogenous double-stranded RNA (dsRNA) is processed by Dicer and Ago2 to form the RNA-induced silencing complex (RISC). The guide strand directs the RISC to the targeted mRNA to silence gene expression by heterochromatin formation, mRNA degradation, or inhibition of transcription or translation. Endogenous miRNAs and shRNAs transcribed in the nucleus are processed by Drosha/DGCR prior to nuclear export by exportin-5 (XPO5). Once in the cytosol, the processed miRNA/shRNA can be incorporated into the RISC to induce genetic silencing. Therapeutic siRNAs introduced to the cell do not need to be processed by Dicer prior to forming the RISC. (Color version of figure is available online.)