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Science
Vol. 297 no. 5589 pp. 2056-2060
DOI: 10.1126/science.1073827
  • Report

A microRNA in a Multiple-Turnover RNAi Enzyme Complex

  1. Phillip D. Zamore*
  1. Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Lazare Research Building, Room 825, 364 Plantation Street, Worcester, MA 01605, USA.

Abstract

In animals, the double-stranded RNA-specific endonuclease Dicer produces two classes of functionally distinct, tiny RNAs: microRNAs (miRNAs) and small interfering RNAs (siRNAs). miRNAs regulate mRNA translation, whereas siRNAs direct RNA destruction via the RNA interference (RNAi) pathway. Here we show that, in human cell extracts, the miRNA let-7 naturally enters the RNAi pathway, which suggests that only the degree of complementarity between a miRNA and its RNA target determines its function. Humanlet-7 is a component of a previously identified, miRNA-containing ribonucleoprotein particle, which we show is an RNAi enzyme complex. Each let-7–containing complex directs multiple rounds of RNA cleavage, which explains the remarkable efficiency of the RNAi pathway in human cells.

  • * To whom correspondence should be addressed. E-mail: phillip.zamore{at}umassmed.edu.

  • Received for publication 10 May 2002.
  • Accepted for publication 22 July 2002.