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Nat Biotechnol. 2008 Aug;26(8):933-40. doi: 10.1038/nbt.1481. Epub 2008 Jul 20.

A small molecule enhances RNA interference and promotes microRNA processing.

Author information

1
Department of Human Genetics, Emory University School of Medicine, 615 Michael St, Atlanta, Georgia 30322, USA.

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.

PMID:
18641635
PMCID:
PMC2831467
DOI:
10.1038/nbt.1481
[Indexed for MEDLINE]
Free PMC Article

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