The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis.
EMBO Rep
; 15(4): 419-27, 2014 Apr.
Article
in 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
RNA-Binding Proteins
/
Apoptosis
/
Alternative Splicing
/
Adaptor Proteins, Signal Transducing
/
DNA-Binding Proteins
/
Bcl-X Protein
Limits:
Humans
Language:
En
Journal:
EMBO Rep
Journal subject:
BIOLOGIA MOLECULAR
Year:
2014
Document type:
Article
Affiliation country: