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

• Tipo: Artigo em Revista Científica Internacional
• Data: 2010

Autores

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

Revista

Título: Cancer Cell

Vol. 18

Páginas: 303-315

ISSN: 1535-6108

Editora: Elsevier

Indexação

ISI Web of Knowledge - 230 Citações

Scopus - 255 Citações

Outras Informações

ID Authenticus: 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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 13