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The transcription factor FBI‐1 inhibits SAM68‐mediated BCL‐X alternative splicing and apoptosis

Pamela Bielli, Roberta Busà, Savino M Di Stasi, Manuel J Munoz, Flavia Botti, Alberto R Kornblihtt, Claudio Sette

Author Affiliations

  1. Pamela Bielli1,2,
  2. Roberta Busà1,2,
  3. Savino M Di Stasi3,
  4. Manuel J Munoz4,
  5. Flavia Botti1,
  6. Alberto R Kornblihtt4 and
  7. Claudio Sette*,1,2
  1. 1Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy
  2. 2Laboratory of Neuroembryology, Fondazione Santa Lucia, Rome, Italy
  3. 3Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy
  4. 4Laboratorio de Fisiologia y Biologia Molecular, Universidad de Buenos Aires, Buenos Aires, Argentina
  1. *Corresponding author. Tel: +39 06 72596260; Fax: +39 06 72596268; E‐mail: claudio.sette{at}
View 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.


Embedded Image

The oncogenic transcription factor FBI‐1 regulates alternative splicing by preventing the splicing regulator SAM68 from binding to BCL‐X mRNA. This increases anti‐apoptotic BCL‐X isoform expression and cell survival.

  • The transcription factor FBI‐1 directly interacts with the splicing regulator SAM68.

  • FBI‐1 impairs binding of SAM68 to BCL‐X mRNA and thus promotes production of the anti‐apoptotic BCL‐X isoform and cell survival.

  • FBI‐1's effect on BCL‐X splicing requires histone deacetylase activity.


  • The authors declare that they have no conflict of interest.

  • Received December 9, 2013.
  • Revision received December 12, 2013.
  • Accepted December 12, 2013.
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