A microRNA in a Multiple-Turnover RNAi Enzyme Complex
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.
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We thank D. Bartel and members of the Zamore laboratory for discussions and comments on the manuscript. We also thank M. Moore for the generous gift of HeLa extracts and G. Dreyfuss for kindly providing antibodies. G. H. is a Charles A. King Trust fellow of the Medical Foundation. P.D.Z. is a Pew Scholar in the Biomedical Sciences and a W. M. Keck Foundation Young Scholar in Medical Research. Supported in part by a grant to P.D.Z. from the National Institutes of Health (GM62862-01).
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Science
Volume 297 | Issue 5589
20 September 2002
20 September 2002
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Received: 10 May 2002
Accepted: 22 July 2002
Published in print: 20 September 2002
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- György Hutvágner,
- Phillip D. Zamore
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