RNA interference (RNAi) is a mechanism for gene silencing that is induced by double-stranded RNA (dsRNA). It is sequence specific and involves the degradation of both dsRNA and single-stranded RNA molecules—usually mRNA—that are homologous in sequence to the dsRNA that triggered the response.
It is thought that RNAi originated as a defense mechanism against viruses. During the normal course of events, cells contain dsDNA and ssRNA but double-stranded RNA is not found. However, during infection by most RNA viruses, the virus genome passes through a double-stranded RNA intermediate (the replicative intermediate). This is true both for viruses that carry their genomes as ssRNA in the virus particle and those that use dsRNA (see Ch. 17 Viruses). Consequently, dsRNA is seen as a signal for infection and triggers an anti-viral response.
RNA interference is triggered by dsRNA that is fully base-paired and is at least 21-23 base pairs in length. Longer molecules of dsRNA are cleaved into fragments of 21-23 bp by a nuclease known as "Dicer" (Fig. 11.11). These RNA fragments are referred to as siRNA (short interfering RNA) and are bound by proteins of the RNA-induced silencing complex (RISC). The RISC complex recognizes and degrades single-stranded RNA that corresponds in sequence to the siRNA. This involves unwinding and strand separation of the siRNA within the RISC complex and subsequent base pairing to the target RNA, as shown in Fig. 11.11. The nuclease activity of the RISC complex, sometimes referred to as "Slicer", then degrades the target RNA.
Dicer Ribonuclease that cleaves double-stranded RNA into segments of 21-23 bp
RNA-induced silencing complex (RISC) Protein complex induced by siRNA that degrades single-stranded RNA corresponding in sequence to the siRNA
RNA interference Response that is triggered by the presence of double-stranded RNA and results in the degradation of mRNA or other RNA
transcripts homologous to the inducing dsRNA short interfering RNA (siRNA) Double-stranded RNA molecules of 21-22 nucleotides involved in triggering RNA interference in eukaryotes Slicer Ribonuclease activity of the RISC complex
Double stranded RNA is normally destroyed by living cells of all organisms.
RNA interference destroys messenger RNA that has the same sequence as double-stranded RNA detected in the cell.
Intruding double-stranded RNA (dsRNA) is recognized (by RDE-4 and other proteins in Caenorhabditis). Dicer cleaves the dsRNA into segments of 21 or 22 nucleotides with one or two base overhangs—short interfering RNA (siRNA). This is recognized by RDE-1 which recruits the RNA-induced silencing complex (RISC). The strands of the siRNA are separated during RISC activation. Finally, RISC cleaves target RNA that corresponds to the siRNA.
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