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. Author manuscript; available in PMC: 2016 Sep 1.
Published in final edited form as: Nat Rev Genet. 2015 Sep;16(9):543–552. doi: 10.1038/nrg3978

Figure 1. Mechanism of gene knockdown by siRNAs.

Figure 1

Exogenously administered small interfering RNAs (siRNAs; double-stranded ~22-nucleotide-long RNA molecules with 2-nucleotide overhangs at the 3´ ends) exploit the endogenous RNA interference (RNAi) machinery. In the endogenous pathway, Dicer generates microRNAs (miRNAs) from RNA hairpins encoded by miRNA genes. The Dicer machinery also processes exogenous double-stranded RNA (dsRNA) sequences containing loops called short hairpin RNAs (shRNAs). Synthetic siRNAs bypass Dicer processing and can directly associate with the RNA-induced silencing complex (RISC) to mediate recognition of target mRNAs through base-pair complementarity. Argonaute 2 in the RISC complex then enzymatically cleaves the target mRNA, leading to target gene knockdown.