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The transcription factor FBI ‐1 inhibits SAM 68‐mediated BCL ‐ X alternative splicing and apoptosis
Author(s) -
Bielli Pamela,
Busà Roberta,
Di Stasi Savino M,
Munoz Manuel J,
Botti Flavia,
Kornblihtt Alberto R,
Sette Claudio
Publication year - 2014
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1002/embr.201338241
Subject(s) - biomedicine , humanities , library science , biology , art , bioinformatics , computer science
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 SAM 68 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 ‐ X L variant and counteracting SAM 68‐mediated apoptosis. Conversely, depletion of FBI ‐1, or expression of a SAM 68 mutant lacking the FBI ‐1 binding region, restores the ability of SAM 68 to induce BCL ‐ X S 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.