Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs

MicroRNAs (miRNAs) are initially expressed as long transcripts that are processed in the nucleus to yield approximately 65-nucleotide (nt) RNA hairpin intermediates, termed pre-miRNAs, that are exported to the cytoplasm for additional processing to yield mature, approximately 22-nt miRNAs. Here, we...

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Bibliographic Details
Published in:Genes & development 2003-12, Vol.17 (24), p.3011-3016
Main Authors: Yi, Rui, Qin, Yi, Macara, Ian G, Cullen, Bryan R
Format: Article
Language:English
Subjects:
Active Transport, Cell Nucleus
Cell Line
Cell Nucleus - genetics
Cell Nucleus - metabolism
Electrophoretic Mobility Shift Assay
Exportin 5
Humans
Karyopherins - genetics
Karyopherins - metabolism
Luciferases - metabolism
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Plasmids
Promoter Regions, Genetic
ran GTP-Binding Protein - metabolism
RAN-GTP protein
Research Communications
RNA - chemistry
RNA - metabolism
RNA Interference
RNA Precursors - genetics
RNA Precursors - metabolism
RNA Processing, Post-Transcriptional
RNA, Messenger - genetics
RNA, Messenger - metabolism
siRNA
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Summary:MicroRNAs (miRNAs) are initially expressed as long transcripts that are processed in the nucleus to yield approximately 65-nucleotide (nt) RNA hairpin intermediates, termed pre-miRNAs, that are exported to the cytoplasm for additional processing to yield mature, approximately 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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.1158803