RNA-induced silencing complex

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RNA-induced silencing complex, or RISC, is a multi-protein siRNA complex which cleaves (incoming viral) dsRNA and binds the antisense RNA strand to a protein which seeks out the complementary strand. When it finds the complementary strand, it activates RNAse activity and cleaves the RNA. This process is important both in gene regulation by micro-RNAs and in defense against viral infections, which often use double-stranded RNA as an infectious vector.

The RNA endonuclease Dicer plays a role in aiding RISC action by providing the intial RNA material to activate the complex as well as the first RNA substrate molecule. When Dicer, which has endonuclease activity against dsRNA and pre-miRNAs, cleaves a pre-miRNA stem-loop or a dsRNA, two complementary short RNA molecules are formed. One strand is integrated into the RISC complex. This strand is known as the guide strand and is selected by the argonaute protein, the catalytically active RNase in the RISC complex, on the basis of the stability of the 5' end.^[1] The remaining strand, known as the anti-guide or passenger strand, is degraded as a RISC complex substrate.^[2] Also degraded are complementary mRNA molecules which induces mRNA degradation. Argonaute proteins are the catalytically active members of the RISC complex and are responsible for the degredation of RNAs complementary to the guide strand of miRNA. It is as yet unclear how the activated RISC complex locates the mRNA targets in the cell, though it has been shown that the process is not coupled to ongoing protein translation from the mRNA.^[3]

[edit] The RISC has a central role in one of the mechanisms of the recycling of RNA into single bases.

[edit] Literature

• The RNA-induced silencing complex is a Mg2+-dependent endonuclease
• Dcr-1 and Dcr-2 have distinct but overlapping roles in the siRNA and miRNA silencing pathways

1. ^ Preall JB, He Z, Gorra JM, Sontheimer EJ. (2006). Short interfering RNA strand selection is independent of dsRNA processing polarity during RNAi in Drosophila. Curr Biol 16(5):530-5.
2. ^ Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. (2005). Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. Cell 123(4):631-40.
3. ^ Sen GL, Wehrman TS, Blau HM. (2005). mRNA translation is not a prerequisite for small interfering RNA-mediated mRNA cleavage. Differentiation 73(6):287-93.