Mini Review ARTICLE
miRNA-like duplexes as RNAi triggers with improved specificity
- 1 Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan
- 2 Department of Medical Genome Sciences, The University of Tokyo, Tokyo, Japan
siRNA duplexes, the most common triggers of RNA interference, are first loaded into an Argonaute (Ago) protein and then undergo unwinding via passenger strand cleavage, which requires the slicer activity of the Ago protein. In mammals, only Ago2 out of the four Ago proteins possesses such slicer activity. In contrast, miRNA/miRNA* duplexes often contain central mismatches that prevent slicer-dependent unwinding. Instead, mismatches in specific regions (seed and 3′-mid regions) promote efficient slicer-independent unwinding by any of the four mammalian Ago proteins. Both slicer-dependent and slicer-independent unwinding mechanisms produce guide-containing RNA-induced silencing complex (RISC), which silences target mRNAs by cleavage, translational repression, and/or deadenylation that leads to mRNA decay. In this review, we summarize our current knowledge of the RISC assembly pathways, and describe a simple method to rationally design artificial miRNA/miRNA*-like duplexes and highlight its benefits to reduce the unwanted “off-target” effects without compromising the specific target silencing activity.
Keywords: Argonaute, RNA-induced silencing complex, RISC, asymmetry
Citation: Betancur JG, Yoda M and Tomari Y (2012) miRNA-like duplexes as RNAi triggers with improved specificity. Front. Gene. 3:127. doi: 10.3389/fgene.2012.00127
Received: 13 April 2012; Accepted: 22 June 2012;
Published online: 12 July 2012.
Edited by:Kumiko Ui-Tei, University of Tokyo, Japan
Reviewed by:Kumiko Ui-Tei, University of Tokyo, Japan
Mohammad Faghihi, Miller School of Medicine, University of Miami, USA
Copyright: © 2012 Betancur, Yoda and Tomari. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
*Correspondence: Yukihide Tomari, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0032, Japan. e-mail:email@example.com
† Juan G. Betancur and Mayuko Yoda have contributed equally to this work.