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

Title
A Genetic Defect in Exportin-5 Traps Precursor MicroRNAs in the Nucleus of Cancer Cells
Type
Article in International Scientific Journal
Year
2010
Authors
Melo, SA
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Moutinho, C
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Ropero, S
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Calin, GA
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Rossi, S
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Spizzo, R
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Fernandez, AF
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Davalos, V
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Villanueva, A
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Montoya, G
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Yamamoto, H
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Schwartz, S
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Esteller, M
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Journal
Title: Cancer CellImported from Authenticus Search for Journal Publications
Vol. 18
Pages: 303-315
ISSN: 1535-6108
Publisher: Elsevier
Other information
Authenticus ID: P-003-1V7
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
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