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A genetic defect in exportin-5 traps precursor microRNAs in the nucleus of cancer cells.

The global impairment of mature microRNAs (miRNAs) is emerging as a common feature of human tumors. One interesting scenario is that defects in the nuclear export of precursor miRNAs (pre-miRNAs) might occur in transformed cells. Exportin 5 (XPO5) mediates pre-miRNA nuclear export and herein we demonstrate the presence of XPO5-inactivating mutations in a subset of human tumors with microsatellite instability. The XPO5 genetic defect traps pre-miRNAs in the nucleus, reduces miRNA processing, and diminishes miRNA-target inhibition. The XPO5 mutant form lacks a C-terminal region that contributes to the formation of the pre-miRNA/XPO5/Ran-GTP ternary complex and pre-miRNAs accumulate in the nucleus. Most importantly, the restoration of XPO5 functions reverses the impaired export of pre-miRNAs and has tumor-suppressor features.

Pubmed ID: 20951941


  • Melo SA
  • Moutinho C
  • Ropero S
  • Calin GA
  • Rossi S
  • Spizzo R
  • Fernandez AF
  • Davalos V
  • Villanueva A
  • Montoya G
  • Yamamoto H
  • Schwartz S
  • Esteller M


Cancer cell

Publication Data

October 19, 2010

Associated Grants

  • Agency: NCI NIH HHS, Id: 1R01CA135444

Mesh Terms

  • Cell Line, Tumor
  • Cell Nucleus
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Karyopherins
  • MicroRNAs
  • Mutant Proteins
  • Mutation
  • Neoplasms
  • Phenotype
  • RNA Precursors
  • RNA Processing, Post-Transcriptional
  • Transfection
  • Tumor Suppressor Proteins
  • ran GTP-Binding Protein