E2F1 controls alternative splicing pattern of genes involved in apoptosis through upregulation of the splicing factor SC35.

Abstract : The transcription factor E2F1 has a key function during S phase progression and apoptosis. It has been well-demonstrated that the apoptotic function of E2F1 involves its ability to transactivate pro-apoptotic target genes. Alternative splicing of pre-mRNAs also has an important function in the regulation of apoptosis. In this study, we identify the splicing factor SC35, a member of the Ser-Rich Arg (SR) proteins family, as a new transcriptional target of E2F1. We demonstrate that E2F1 requires SC35 to switch the alternative splicing profile of various apoptotic genes such as c-flip, caspases-8 and -9 and Bcl-x, towards the expression of pro-apoptotic splice variants. Finally, we provide evidence that E2F1 upregulates SC35 in response to DNA-damaging agents and show that SC35 is required for apoptosis in response to these drugs. Taken together, these results demonstrate that E2F1 controls pre-mRNA processing events to induce apoptosis and identify the SC35 SR protein as a key direct E2F1-target in this setting.
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Galina Merdzhanova, Sandrine de Seranno, Arnaud van den Broeck, Laurent Corcos, Christian Brambilla, et al.. E2F1 controls alternative splicing pattern of genes involved in apoptosis through upregulation of the splicing factor SC35.. Cell Death and Differentiation, Nature Publishing Group, 2008, 15 (12), pp.1815-23. ⟨10.1038/cdd.2008.135⟩. ⟨inserm-02345442⟩

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