KORNBLIHTT Alberto Rodolfo
The transcription factor FBI-1 inhibits SAM68-mediated BCL-X alternative splicing and apoptosis
BIELLI, P; BUSÀ, R; DI STASI, S. ; MUÑOZ, M. J.; BOTTI, F.; KORNBLIHTT, A. R; SETTE, C.
NATURE PUBLISHING GROUP
Lugar: Londres; Año: 2014 vol. 15 p. 419 - 419
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 pharmacologi- cal inhibition recapitulates the effects of FBI-1 knockdown. Our study reveals an unexpected function for FBI-1 in splicing modula- tion with a direct impact on cell survival.