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MicroRNAs direct rapid deadenylation of mRNA
- *Skirball Institute of Biomolecular Medicine and
- †Department of Microbiology, New York University School of Medicine, New York, NY 10016
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Edited by Stanley N. Cohen, Stanford University School of Medicine, Stanford, CA, and approved January 19, 2006 (received for review December 18, 2005)
Abstract
MicroRNAs (miRNAs) are ubiquitous regulators of eukaryotic gene expression. In addition to repressing translation, miRNAs can down-regulate the concentration of mRNAs that contain elements to which they are imperfectly complementary. Using miR-125b and let-7 as representative miRNAs, we show that in mammalian cells this reduction in message abundance is a consequence of accelerated deadenylation, which leads to rapid mRNA decay. The ability of miRNAs to expedite poly(A) removal does not result from decreased translation; nor does translational repression by miRNAs require a poly(A) tail, a 3′ histone stem-loop being an effective substitute. These findings suggest that miRNAs use two distinct posttranscriptional mechanisms to down-regulate gene expression.
Footnotes
- ‡To whom correspondence should be addressed at: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016. E-mail: belasco{at}saturn.med.nyu.edu
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Author contributions: L.W. and J.G.B. designed research; L.W. performed research; L.W., J.F., and J.G.B. analyzed data; and L.W. and J.G.B. wrote the paper.
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Conflict of interest statement: No conflicts declared.
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This paper was submitted directly (Track II) to the PNAS office.
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See Commentary on page 3951.
- Abbreviation:
- miRNA,
- microRNA.
- © 2006 by The National Academy of Sciences of the USA
