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 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.
Yi
Rui
R
Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
Qin
Yi
Y
Macara
Ian G
IG
Cullen
Bryan R
BR
D021581:Active Transport, Cell Nucleus; D002460:Cell Line; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012313:RNA / Q000737:chemistry* / Q000378:metabolism*; D034622:RNA Interference; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000378:metabolism
D028884:Karyopherins; D035683:MicroRNAs; D012322:RNA Precursors; D012333:RNA, Messenger; C446511:XPO5 protein, human; D012313:RNA; D008156:Luciferases; D020931:ran GTP-Binding Protein