Article abstract


Nature Biotechnology 26, 933 - 940 (2008)
Published online: 20 July 2008 | doi:10.1038/nbt.1481

A small molecule enhances RNA interference and promotes microRNA processing

Ge Shan1,6, Yujing Li1,6, Junliang Zhang2, Wendi Li1, Keith E Szulwach1, Ranhui Duan1, Mohammad A Faghihi3, Ahmad M Khalil3, Lianghua Lu2, Zain Paroo4, Anthony W S Chan1, Zhangjie Shi5, Qinghua Liu4, Claes Wahlestedt3, Chuan He2 & Peng Jin1


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.

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  1. Department of Human Genetics, Emory University School of Medicine, 615 Michael St., Atlanta, Georgia 30322, USA.
  2. Department of Chemistry, The University of Chicago, 929 East 57th St., Chicago, Illinois 60637, USA.
  3. Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, 5353 Parkside Drive, Jupiter, Florida 33458, USA.
  4. Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390, USA.
  5. The College of Chemistry, Peking University, 202 Chengfu Rd., Beijing, 100871, P.R. China.
  6. These authors contributed equally to this work.

Correspondence to: Peng Jin1 e-mail: pjin@genetics.emory.edu



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