Author/Authors :
Melo، نويسنده , , Sonia A. and Moutinho، نويسنده , , Catia and Ropero، نويسنده , , Santiago and Calin، نويسنده , , George A. and Rossi، نويسنده , , Simona and Spizzo، نويسنده , , Riccardo and Fernandez، نويسنده , , Agustin F. and Davalos، نويسنده , , Veronica and Villanueva، نويسنده , , Alberto and Montoya، نويسنده , , Guillermo and Yamamoto، نويسنده , , Hiroyuki and Schwartz Jr.، نويسنده , , Simo and Esteller، نويسنده , , Manel، نويسنده ,
Abstract :
Summary
obal 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.
