RNA-induced silencing complex
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2008-06-22T16:28:02Z
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'''RNA-induced silencing complex''', or '''RISC''', is a multi-protein [[siRNA]] complex which cleaves (incoming viral) [[dsRNA]] and binds short [[antisense]] RNA strands which are then able to bind complementary strands. When it finds the complementary strand, it activates [[RNAse]] activity and cleaves the RNA. This process is important both in gene regulation by [[micro-RNA]]s and in defense against viral infections, which often use double-stranded RNA as an infectious vector.
==Strands==
The RNA [[endonuclease]] [[Dicer]] plays a role in aiding RISC action by providing the initial RNA material to activate the complex as well as the first RNA substrate molecule.
When Dicer, which has endonuclease activity against [[dsRNA]] and pre-[[miRNA]]s, cleaves a pre-miRNA stem-loop or a dsRNA, a 20-25 [[base pair]] double-stranded RNA fragment is formed with a 2 nucleotide 3' overhang at each end.<ref name="Zamore">{{cite journal |author=Zamore P, Tuschl T, Sharp P, Bartel D |title=RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals |journal=Cell |volume=101 |issue=1 |pages=25–33 |year=2000 |pmid=10778853 |doi=10.1016/S0092-8674(00)80620-0}}</ref><ref name="Vermeulen">{{cite journal |author=Vermeulen A, Behlen L, Reynolds A, Wolfson A, Marshall W, Karpilow J, Khvorova A |title=The contributions of dsRNA structure to dicer specificity and efficiency |journal=RNA |volume=11 |issue=5 |pages=674–82 |year=2005 |pmid=15811921 |doi=10.1261/rna.7272305}}</ref>
* 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.<ref name="Preall">Preall JB, He Z, Gorra JM, Sontheimer EJ. (2006). "Short Interfering RNA Strand Selection Is Independent of dsRNA Processing Polarity during RNAi in <i>Drosophila</I>." ''Curr Biol'' 16(5):530-5.</ref>
* The remaining strand, known as the anti-guide or passenger strand, is degraded as a RISC complex substrate.<ref name="Gregory">Gregory RI, Chendrimada TP, Cooch N, Shiekhattar R. (2005). Human RISC couples microRNA biogenesis and posttranscriptional gene silencing. ''Cell'' 123(4):631-40.</ref>
==Binding==
The RISC complex with a bound siRNA recognizes [[complementarity (molecular biology)|complementary]] [[messenger RNA]] (mRNA) molecules and degrades them, resulting in substantially decreased levels of [[translation (biology)|protein translation]] and effectively turning off the gene. 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.<ref name="Sen">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. </ref> Endogenously expressed miRNA is usually imperfectly complementary to a large number of nuclear genes and has a modulating effect on these genes' levels of expression via [[translation (genetics)|translational repression]].<ref name="Saumet">{{cite journal |author=Saumet A, Lecellier CH |year=2006 |title= Anti-viral RNA silencing: do we look like plants?|journal=Retrovirology |volume=3 |issue=3 |pmid=16409629 |url=http://www.retrovirology.com/content/3/1/3 |doi= 10.1186/1742-4690-3-3 |pages= 3 }}</ref>
==References==
{{Reflist|2}}
==External links==
* {{cite journal |author=Schwarz DS, Tomari Y, Zamore PD |title=The RNA-induced silencing complex is a Mg2+-dependent endonuclease |journal=Curr. Biol. |volume=14 |issue=9 |pages=787–91 |year=2004 |pmid=15120070 |doi=10.1016/j.cub.2004.03.008}}
* [http://www.signaling-gateway.org/update/updates/200405/nrm1387.html Dcr-1 and Dcr-2 have distinct but overlapping roles in the siRNA and miRNA silencing pathways]
* {{MeshName|RNA-Induced+Silencing+Complex}}
{{Nucleases}}
[[Category:RNA]]
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