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Molecular Basis for Target RNA Recognition and Cleavage by Human RISC

Molecular Basis for Target RNA Recognition and Cleavage by Human RISC

Authors :
Ameres, Stefan Ludwig
Martinez, Javier
Schroeder, ReneE
Source :
Cell. July 13, 2007, Vol. 130 Issue 1, p101, 12 p.
Publication Year :
2007

Abstract

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cell.2007.04.037 Byline: Stefan Ludwig Ameres (1), Javier Martinez (2), Renee Schroeder (1) Keywords: PROTEINS; RNA Abstract: The RNA-Induced Silencing Complex (RISC) is a ribonucleoprotein particle composed of a single-stranded short interfering RNA (siRNA) and an endonucleolytically active Argonaute protein, capable of cleaving mRNAs complementary to the siRNA. The mechanism by which RISC cleaves a target RNA is well understood, however it remains enigmatic how RISC finds its target RNA. Here, we show, both in vitro and in vivo, that the accessibility of the target site correlates directly with the efficiency of cleavage, demonstrating that RISC is unable to unfold structured RNA. In the course of target recognition, RISC transiently contacts single-stranded RNA nonspecifically and promotes siRNA-target RNA annealing. Furthermore, the 5' part of the siRNA within RISC creates a thermodynamic threshold that determines the stable association of RISC and the target RNA. We therefore provide mechanistic insights by revealing features of RISC and target RNAs that are crucial to achieve efficiency and specificity in RNA interference. Author Affiliation: (1) Max F. Perutz Laboratories, University of Vienna, Dr.-Bohr-Gasse 9/5, A-1030 Vienna, Austria (2) Institute of Molecular Biotechnology of the Austrian Academy of Sciences, IMBA, Dr.-Bohr-Gasse 3-5, A-1030 Vienna, Austria Article History: Received 15 November 2006; Revised 14 March 2007; Accepted 24 April 2007 Article Note: (miscellaneous) Published: July 12, 2007

Details

Language :
English
ISSN :
00928674
Volume :
130
Issue :
1
Database :
Gale General OneFile
Journal :
Cell
Publication Type :
Academic Journal
Accession number :
edsgcl.166446408