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Cancer Cell. 2010 Oct 19;18(4):303-15. doi: 10.1016/j.ccr.2010.09.007.

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

Author information

1
Bellvitge Biomedical Research Institute, Barcelona, Catalonia, Spain.

Abstract

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.

PMID:
20951941
DOI:
10.1016/j.ccr.2010.09.007
[Indexed for MEDLINE]
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