Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs
- 1 Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA
- 2 Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
- 3 Center for Cell Signaling, University of Virginia, Charlottesville, Virginia 22908, USA
Abstract
MicroRNAs (miRNAs) are initially expressed as long transcripts that are processed in the nucleus to yield ∼65-nucleotide (nt) RNA hairpin intermediates, termed pre-miRNAs, that are exported to the cytoplasm for additional processing to yield mature, ∼22-nt miRNAs. Here, we demonstrate that human pre-miRNA nuclear export, and miRNA function, are dependent on Exportin-5. Exportin-5 can bind pre-miRNAs specifically in vitro, but only in the presence of the Ran-GTP cofactor. Short hairpin RNAs, artificial pre-miRNA analogs used to express small interfering RNAs, also depend on Exportin-5 for nuclear export. Together, these findings define an additional cellular cofactor required for miRNA biogenesis and function.
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Footnotes
Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1158803.
↵4Corresponding author. E-MAILculle002{at}mc.duke.edu; FAX (919) 681-8979.
- Accepted October 28, 2003.
- Received October 7, 2003.
- Cold Spring Harbor Laboratory Press
