A. On entering the cell, endogenously transcribed or exogenously introduced long dsRNA acts as a trigger of the RNAi process.
B. It is first processed by the RNase III enzyme Dicer in an ATP-dependent reaction.
C. Dicer processes long dsRNA into 21-23 nt siRNA with 2-nt 3' overhangs. siRNA can also be synthesized outside a cell and then be introduced into a cell through the process of transfection or electroporation.
D. The siRNA are incorporated into the RISC RNAi effector complex which consists of an Argonaute (Ago) protein as one of its main components. Ago cleaves and discards the passenger (sense) strand of the siRNA duplex leading to an active RISC.
E and F. The remaining (antisense) strand of the siRNA duplex serves as the guide strand and guides the RISC to its homologous mRNA, resulting in the endonucleolytic cleavage of the target mRNA.