What is RNAi
RNA interference (RNAi) is a highly evolutionally conserved process of post-transcriptional gene silencing (PTGS) by which double stranded RNA (dsRNA), when introduced into a cell, causes sequence-specific degradation of homogolous mRNA sequences. It was first discovered in 1998 by Andrew Fire and Craig Mello in the nematode worm Caenorhabditis elegans and later found in a wide variety of organisms, including mammals.
Mechanism of RNA interference
A. On entering the cell, long dsRNAs act as a trigger of RNAi process.
B. It is first processed by the RNAse III enzyme Dicer in an ATP-dependent reaction.
C. Dicer processes dsRNAs into 21-23 nt short interfering RNA (siRNA) with 2-nt 3' overhangs. siRNA can also be synthesized outside the cell and then be introduced into a cell.
D. The siRNAs are incorporated into the RNA-inducing silencing complex (RISC) 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 activation of the RISC.
E and F. The remaining guide (antisense) strand of the siRNA guides RISC to its homologous mRNA, resulting in the endonucleolytic cleavage of the target mRNA
