Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs (original) (raw)
- Rui Yi2,
- Yi Qin3,
- Ian G. Macara3, and
- Bryan R. Cullen1,2,4
- 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.
Footnotes
Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1158803.
↵4 Corresponding author. E-MAIL culle002{at}mc.duke.edu; FAX (919) 681-8979.
- Accepted October 28, 2003.
- Received October 7, 2003.
Cold Spring Harbor Laboratory Press