Fig. 2

RNA silencing mechanism. For therapeutic RNAi applications, a lentiviral vector or plasmid is transcribed by RNA pol III into shRNA. This shRNA is then exported from the nucleus to the cytoplasm by Exportin 5. After export, shRNA or miRNA are processed by Dicer and loaded into RISC. For exogenously delivered siRNA or Dicer substrate RNA (dsiRNA), the processed siRNA is loaded directly into RISC. The passenger strand is removed from the guide strand and RISC guides the remaining strand to its complementary mRNA target. RISC then cleaves the mRNA for degradation. Abbreviations: pol III, RNA polymerase III; pol II, RNA polymerase II; RISC, RNA-induced silencing complex; shRNA, short hairpin RNA; siRNA, short interfering RNA