A Genetic Defect in Exportin-5 Traps Precursor MicroRNAs in the Nucleus of Cancer Cells

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Melo, SA (Author) Other; Moutinho, C (Author) Other; Ropero, S (Author) Other; Calin, GA (Author) Other; Rossi, S (Author) Other; Spizzo, R (Author) Other; Fernandez, AF (Author) Other; Davalos, V (Author) Other; Villanueva, A (Author) Other; Montoya, G (Author) Other; Yamamoto, H (Author) Other; Schwartz, S (Author) Other; Esteller, M (Author) Other

Journal

Title: Cancer Cell

Vol. 18

Pages: 303-315

ISSN: 1535-6108

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 230 Citations

Scopus - 255 Citations

Other information

Authenticus ID: P-003-1V7

DOI: 10.1016/j.ccr.2010.09.007

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13