title: MBNL1 and RBFOX2 cooperate to establish a splicing programme involved in pluripotent stem cell differentiation.
abstract: 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.
authors.affiliation: 1] CNRS, Institut de Génétique Moléculaire de Montpellier, Montpellier F-34293, France [2] Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne NE1 3BZ, UK [3] Université Montpellier 2, F-34293 Montpellier cedex 5, France [4] Université Montpellier 1, F-34094 Montpellier cedex 5, France [5].
authors.forename: Julian P
authors.initials: JP
authors.lastname: Venables
authors.forename: Laure
authors.initials: L
authors.lastname: Lapasset
authors.forename: Gilles
authors.initials: G
authors.lastname: Gadea
authors.forename: Philippe
authors.initials: P
authors.lastname: Fort
authors.forename: Roscoe
authors.initials: R
authors.lastname: Klinck
authors.forename: Manuel
authors.initials: M
authors.lastname: Irimia
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Vignal
authors.forename: Philippe
authors.initials: P
authors.lastname: Thibault
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Prinos
authors.forename: Benoit
authors.initials: B
authors.lastname: Chabot
authors.forename: Sherif
authors.initials: S
authors.lastname: Abou Elela
authors.forename: Pierre
authors.initials: P
authors.lastname: Roux
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Lemaitre
authors.forename: Jamal
authors.initials: J
authors.lastname: Tazi
mesh_terms: D017398:Alternative Splicing; D002454:Cell Differentiation; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D007231:Infant, Newborn; D008648:Mesoderm / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D011485:Protein Binding; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C493663:MBNL1 protein, human; C454924:RBFOX2 protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins; D012097:Repressor Proteins