MBNL1 and RBFOX2 cooperate to establish a splicing programme involved in pluripotent stem cell differentiation

Julian Venables , Laure Lapasset (1) , Gilles Gadea (2) , Philippe Fort (3) , Roscoe Klinck (4) , Manuel Irimia , Emmanuel Vignal (3) , Philippe Thibault (5) , Panagiotis Prinos , Benoit Chabot (5) , Sherif Abou Elela (5) , Pierre Roux (3) , Jean-Marc Lemaitre (1) , Jamal Tazi (6)

1 IGF - Institut de Génomique Fonctionnelle
2 PIMIT - Processus Infectieux en Milieu Insulaire Tropical
3 CRBM - Centre de recherche en Biologie Cellulaire
4 Laboratoire de Génomique Fonctionnelle
5 UdeS - Université de Sherbrooke
6 Centre Nationale de Recherche Scientifique

Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) has provided huge insight into the pathways, mechanisms and transcription factors that control differentiation. Here we use high-throughput RT-PCR technology to take a snapshot of splicing changes in the full spectrum of high-and low-expressed genes during induction of fibroblasts, from several donors, into iPSCs and their subsequent redifferentiation. We uncover a programme of concerted alternative splicing changes involved in late mesoderm differentiation and controlled by key splicing regulators MBNL1 and RBFOX2. These critical splicing adjustments arise early in vertebrate evolution and remain fixed in at least 10 genes (including PLOD2, CLSTN1, ATP2A1, PALM, ITGA6, KIF13A, FMNL3, PPIP5K1, MARK2 and FNIP1), implying that vertebrates require alternative splicing to fully implement the instructions of transcriptional control networks.

Domaines: Biologie moléculaire; Embryologie et organogenèse; Cancer; Systématique, phylogénie et taxonomie; Organisation et fonctions cellulaires [q-bio.SC]

Julian Venables, Laure Lapasset, Gilles Gadea, Philippe Fort, Roscoe Klinck, et al.. MBNL1 and RBFOX2 cooperate to establish a splicing programme involved in pluripotent stem cell differentiation. Nature Communications, 2013, 4 (1), ⟨10.1038/ncomms3480⟩. ⟨hal-02267336⟩