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Published Online November 20, 2003
Science DOI: 10.1126/science.1090599

Reports

Submitted on August 19, 2003
Accepted on October 30, 2003

Nuclear Export of MicroRNA Precursors

Elsebet Lund 1, Stephan Güttinger 2, Angelo Calado 3, James E. Dahlberg 1*, Ulrike Kutay 2*

1 Department of Biomolecular Chemistry, University of Wisconsin Medical School, Madison, WI 53706 USA.
2 Institute of Biochemistry, Swiss Federal Institute of Technology, Zurich, CH-8093 Switzerland.
3 Institute of Biochemistry, Swiss Federal Institute of Technology, Zurich, CH-8093 Switzerland; Present address: Instituto de Bioquimica, Universidade de Lisboa, Av. Prof. Egas Moniz, Lisboa, Portugal.

* To whom correspondence should be addressed. E-mail: dahlberg{at}wisc.edu, ulrike.kutay{at}bc.biol.ethz.ch.

MicroRNAs (miRNAs), which function as regulators of gene expression in eukaryotes, are processed from larger transcripts by sequential action of nuclear and cytoplasmic RNAse III-like endonucleases. We show that Exportin-5 (Exp5) mediates efficient nuclear export of short miRNA precursors (pre-miRNAs), and its depletion by RNAi results in reduced miRNA levels. Exp5 binds correctly processed pre-miRNAs directly and specifically, in a RanGTP-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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