A small molecule enhances RNA interference and promotes microRNA processing

• Type of Material: Article
• Authors: Ge Shan, Emory University; Yujing Li, Emory University; Junliang Zhang, The University of Chicago; Wendi Li, Emory University; Keith E. Szulwach, Emory University; Ranhui Duan, Emory University; Mohammad A Faghihi, The Scripps Research Institute; Ahmad M Khalil, The Scripps Research Institute; Lianghua Lu, The University of Chicago; Zain Paroo, University of Texas Southwestern Medical Center; Anthony Chan, Emory University; Zhangjie Shi, Peking University; Qinghua Liu, University of Texas Southwestern Medical Center; Claes Wahlestedt, The Scripps Research Institute; Chuan He, The University of Chicago; Peng Jin, Emory University
• Language: English
• Date: 2008-08
• Publisher: Nature Research (part of Springer Nature)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2008 Nature Publishing Group
• Final Published Version (URL): http://www.nature.com/nbt/journal/v26/n8/full/nbt.1481.html
• Title of Journal or Parent Work: Nature Biotechnology
• ISSN: 1087-0156
• Volume: 26
• Issue: 8
• Start Page: 933
• End Page: 940
• Grant/Funding Information: Q.L. is a Damon Runyon Scholar (DRS-43) and is supported by the Welch Foundation (I-1608).; P.J. is the recipient of a Beckman Young Investigator Award and a Basil O’Connor Scholar Research Award and is an Alfred P. Sloan Research Fellow in Neuroscience.; P.J. is supported by NIH grants (NS051630 and MH076090).
• Research Categories: Chemistry, Biochemistry; Biology, Cell; Biology, Molecular

Abstract

Small interfering RNAs (siRNAs) and microRNAs (miRNAs) are sequence-specific post-transcriptional regulators of gene expression. Although major components of the RNA interference (RNAi) pathway have been identified, regulatory mechanisms for this pathway remain largely unknown. Here we demonstrate that the RNAi pathway can be modulated intracellularly by small molecules. We have developed a cell-based assay to monitor the activity of the RNAi pathway and find that the small-molecule enoxacin (Penetrex) enhances siRNA-mediated mRNA degradation and promotes the biogenesis of endogenous miRNAs. We show that this RNAi-enhancing activity depends on the trans-activation-responsive region RNA-binding protein. Our results provide a proof-of-principle demonstration that small molecules can be used to modulate the activity of the RNAi pathway. RNAi enhancers may be useful in the development of research tools and therapeutics.