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

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  • Julian P. Venables

    (CNRS, Institut de Génétique Moléculaire de Montpellier
    Institute of Genetic Medicine, Newcastle University
    Université Montpellier 2
    Université Montpellier 1)

  • Laure Lapasset

    (CNRS, Institut de Génétique Moléculaire de Montpellier
    Université Montpellier 2
    Université Montpellier 1
    CNRS, Institut de Génomique Fonctionnelle de Montpellier)

  • Gilles Gadea

    (Université Montpellier 2
    Université Montpellier 1
    CNRS, Centre de Recherche de Biochimie Macromoléculaire de Montpellier)

  • Philippe Fort

    (Université Montpellier 2
    Université Montpellier 1
    CNRS, Centre de Recherche de Biochimie Macromoléculaire de Montpellier)

  • Roscoe Klinck

    (Laboratoire de Génomique Fonctionnelle de l’Université de Sherbrooke
    Faculté de médecine et des sciences de la santé, Université de Sherbrooke)

  • Manuel Irimia

    (University of Toronto)

  • Emmanuel Vignal

    (Université Montpellier 2
    Université Montpellier 1
    CNRS, Centre de Recherche de Biochimie Macromoléculaire de Montpellier)

  • Philippe Thibault

    (Laboratoire de Génomique Fonctionnelle de l’Université de Sherbrooke)

  • Panagiotis Prinos

    (Laboratoire de Génomique Fonctionnelle de l’Université de Sherbrooke)

  • Benoit Chabot

    (Laboratoire de Génomique Fonctionnelle de l’Université de Sherbrooke
    Faculté de médecine et des sciences de la santé, Université de Sherbrooke)

  • Sherif Abou Elela

    (Laboratoire de Génomique Fonctionnelle de l’Université de Sherbrooke
    Faculté de médecine et des sciences de la santé, Université de Sherbrooke)

  • Pierre Roux

    (Université Montpellier 2
    Université Montpellier 1
    CNRS, Centre de Recherche de Biochimie Macromoléculaire de Montpellier)

  • Jean-Marc Lemaitre

    (Université Montpellier 2
    Université Montpellier 1
    CNRS, Institut de Génomique Fonctionnelle de Montpellier
    INSERM)

  • Jamal Tazi

    (CNRS, Institut de Génétique Moléculaire de Montpellier
    Université Montpellier 2
    Université Montpellier 1)

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.

Suggested Citation

  • Julian P. Venables & Laure Lapasset & Gilles Gadea & Philippe Fort & Roscoe Klinck & Manuel Irimia & Emmanuel Vignal & Philippe Thibault & Panagiotis Prinos & Benoit Chabot & Sherif Abou Elela & Pierr, 2013. "MBNL1 and RBFOX2 cooperate to establish a splicing programme involved in pluripotent stem cell differentiation," Nature Communications, Nature, vol. 4(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3480
    DOI: 10.1038/ncomms3480
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    Cited by:

    1. Nicole D. Moss & Kristen L. Wells & Alexandra Theis & Yong-Kyung Kim & Aliya F. Spigelman & Xiong Liu & Patrick E. MacDonald & Lori Sussel, 2023. "Modulation of insulin secretion by RBFOX2-mediated alternative splicing," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Michelle Maurin & Mohammadreza Ranjouri & Cristina Megino-Luque & Justin Y. Newberg & Dongliang Du & Katelyn Martin & Robert E. Miner & Mollie S. Prater & Dave Keng Boon Wee & Barbara Centeno & Shondr, 2023. "RBFOX2 deregulation promotes pancreatic cancer progression and metastasis through alternative splicing," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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