Nuclear Export of MicroRNA Precursors
Abstract
MicroRNAs (miRNAs), which function as regulators of gene expression in eukaryotes, are processed from larger transcripts by sequential action of nuclear and cytoplasmic ribonuclease III–like endonucleases. We show that Exportin-5 (Exp5) mediates efficient nuclear export of short miRNA precursors (pre-miRNAs) and that its depletion by RNA interference results in reduced miRNA levels. Exp5 binds correctly processed pre-miRNAs directly and specifically, in a Ran guanosine triphosphate–dependent manner, but interacts only weakly with extended pre-miRNAs that yield incorrect miRNAs when processed by Dicer in vitro. Thus, Exp5 is key to miRNA biogenesis and may help coordinate nuclear and cytoplasmic processing steps.
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We thank E. White and B. Clark for technical assistance; M. Olson, H. Allawi, V. Lyamichev, and S. Olson of Third Wave Technologies Inc. Madison, WI for help with Invader assays; C. B. Jensen for initiating in vitro Dicer experiments; and G. Lipowsky and S. Hasan for critically reading the manuscript. UK is supported by the Swiss National Science Foundation, and J.E.D. and E.L. are supported by NIH grant GM-30220. J.E.D and E.L. have a financial interest in Third Wave Technologies Inc.
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Science
Volume 303 | Issue 5654
2 January 2004
2 January 2004
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American Association for the Advancement of Science.
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Submission history
Received: 19 August 2003
Accepted: 30 October 2003
Published in print: 2 January 2004
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