Figure 5.

Schematic representation of siRNA mediated gene silencing. Long dsRNA is cleaved by enzyme Dicer into 20–30 bp siRNA, which consists of a passenger strand (sense) and a guide strand (antisense). Alternatively, a mature siRNA containing a 5′ phosphate and a two-nucleotide overhang at the 3′ end can be delivered to cells. The multiprotein enzyme complex RISC recognizes the siRNA in the cytoplasm, unwinds the duplex siRNA and incorporates the guide strand (antisense) while the passenger strand is released. RISC then uses the guide strand to specifically target mRNA. For perfectly matching targets, the endonuclease Ago 2 within RISC induces one cleavage that takes place at position 10 upstream of the 5′ end. After cleavage, the siRNA-RISC complex is recycled to target other mRNA.