A small molecule enhances RNA interference and promotes microRNA processing

Ge Shan, Yujing Li, Junliang Zhang, Wendi Li, Keith E. Szulwach, Ranhui Duan, Mohammad A. Faghihi, Ahmad M. Khalil, Lianghua Lu, Zain Paroo, Anthony W.S. Chan, Zhangjie Shi, Qinghua Liu, Claes Wahlestedt, Chuan He, Peng Jin

Research output: Contribution to journalArticle

161 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)933-940
Number of pages8
JournalNature Biotechnology
Volume26
Issue number8
DOIs
StatePublished - Aug 2008

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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  • Cite this

    Shan, G., Li, Y., Zhang, J., Li, W., Szulwach, K. E., Duan, R., Faghihi, M. A., Khalil, A. M., Lu, L., Paroo, Z., Chan, A. W. S., Shi, Z., Liu, Q., Wahlestedt, C., He, C., & Jin, P. (2008). A small molecule enhances RNA interference and promotes microRNA processing. Nature Biotechnology, 26(8), 933-940. https://doi.org/10.1038/nbt.1481