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A genetic defect in exportin-5 traps precursor micro RNAs in the nucleus of cancer cells


A genetic defect in exportin-5 traps precursor micro RNAs in the nucleus of cancer cells



Cancer Cell 18(4): 303-315



ISSN/ISBN: 1535-6108

PMID: 20951941

DOI: 10.1016/j.ccr.2010.09.007

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.

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Accession: 051139731

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