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

Genes Dev. 2003 Dec 15;17(24):3011-6. doi: 10.1101/gad.1158803. Epub 2003 Dec 17.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus
  • Cell Line
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Humans
  • Karyopherins / genetics
  • Karyopherins / metabolism*
  • Luciferases / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Plasmids
  • Promoter Regions, Genetic
  • RNA / chemistry*
  • RNA / metabolism*
  • RNA Interference
  • RNA Precursors / genetics
  • RNA Precursors / metabolism
  • RNA Processing, Post-Transcriptional*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • ran GTP-Binding Protein / metabolism

Substances

  • Karyopherins
  • MicroRNAs
  • RNA Precursors
  • RNA, Messenger
  • XPO5 protein, human
  • RNA
  • Luciferases
  • ran GTP-Binding Protein