The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis.
EMBO Rep
; 15(4): 419-27, 2014 Apr.
Article
em En
| MEDLINE
| ID: mdl-24514149
ABSTRACT
Alternative splicing (AS) is tightly coupled to transcription for the majority of human genes. However, how these two processes are linked is not well understood. Here, we unveil a direct role for the transcription factor FBI-1 in the regulation of AS. FBI-1 interacts with the splicing factor SAM68 and reduces its binding to BCL-X mRNA. This, in turn, results in the selection of the proximal 5' splice site in BCL-X exon 2, thereby favoring the anti-apoptotic BCL-XL variant and counteracting SAM68-mediated apoptosis. Conversely, depletion of FBI-1, or expression of a SAM68 mutant lacking the FBI-1 binding region, restores the ability of SAM68 to induce BCL-XS splicing and apoptosis. FBI-1's role in splicing requires the activity of histone deacetylases, whose pharmacological inhibition recapitulates the effects of FBI-1 knockdown. Our study reveals an unexpected function for FBI-1 in splicing modulation with a direct impact on cell survival.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Proteínas de Ligação a RNA
/
Apoptose
/
Processamento Alternativo
/
Proteínas Adaptadoras de Transdução de Sinal
/
Proteínas de Ligação a DNA
/
Proteína bcl-X
Limite:
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article