Mechanisms of RNA interference (RNAi). RNAi is triggered by long double-stranded RNA (dsRNA), small interfering RNA (siRNA), plasmid or virus-based short hairpin RNA (shRNA), or microRNA (miRNA), and siRNA. Long dsRNA, shRNA, and pre-miRNA are processed by Dicer into 21–23-nt siRNA duplexes with symmetric 2-nt 3′ overhangs and 5′-phosphate groups. Processed siRNAs assemble with cellular proteins to form an RNA-induced silencing complex (RISC). During RISC assembly, one strand (passenger) is eliminated, while the other strand (guide) produces an active RISC, which eventually triggers the sequence-specific mRNA degradation (in case of total complementarity) or translational repression (in case of incorporation of partially complementary miRNA).
