My road to alternative splicing control: from simple paths to loops and interconnections

Abstract

With the functional importance of alternative splicing being validated in nearly every mammalian biological system and implicated in many human diseases, it is now crucial to identify the molecular programs that control the production of splice variants. In this article, I will survey how our knowledge of the basic principles of alternative splicing control evolved over the last 25 years. I will also describe how investigation of the splicing control of an apoptotic regulator led us to identify novel effectors and revealed the existence of converging pathways linking splicing decisions to DNA damage. Finally, I will review how our efforts at developing tools designed to monitor and redirect splicing helped assess the impact of misregulated splicing in cancer.

Keywords: RNA binding proteins; alternative splicing; apoptose; apoptosis; cancer; protéines liant l’ARN; splicing; épissage; épissage alternatif.