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Polypyrimidine Tract Binding Proteins are essential for B cell development

View ORCID ProfileElisa Monzón-Casanova, Louise S. Matheson, Kristina Tabbada, View ORCID ProfileKathi Zarnack, Christopher W. J. Smith, View ORCID ProfileMartin Turner
doi: https://doi.org/10.1101/769141
Elisa Monzón-Casanova
1Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK
2Department of Biochemistry, University of Cambridge, Cambridge, UK
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  • ORCID record for Elisa Monzón-Casanova
  • For correspondence: elisa.monzon-casanova@babraham.ac.uk martin.turner@babraham.ac.uk
Louise S. Matheson
1Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK
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Kristina Tabbada
3Next Generation Sequencing Facility, The Babraham Institute, Cambridge, UK
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Kathi Zarnack
4Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Frankfurt am Main, Germany
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  • ORCID record for Kathi Zarnack
Christopher W. J. Smith
2Department of Biochemistry, University of Cambridge, Cambridge, UK
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Martin Turner
1Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK
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  • ORCID record for Martin Turner
  • For correspondence: elisa.monzon-casanova@babraham.ac.uk martin.turner@babraham.ac.uk
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Abstract

Polypyrimidine Tract Binding Protein 1 (PTBP1) is a RNA-binding protein (RBP) expressed throughout B cell development. Deletion of Ptbp1 in mouse pro-B cells results in upregulation of PTBP2 and normal B cell development. We show that PTBP2 compensates for PTBP1 in B cell ontogeny as deletion of both Ptbp1 and Ptbp2 results in a complete block at the pro-B cell stage and a lack of mature B cells. In pro-B cells PTBP1 ensures precise synchronisation of the activity of cyclin dependent kinases at distinct stages of the cell cycle, suppresses S-phase entry and promotes progression into mitosis. PTBP1 controls mRNA abundance and alternative splicing of important cell cycle regulators including CYCLIN-D2, c-MYC, p107 and CDC25B. Our results reveal a previously unrecognised mechanism mediated by a RBP that is essential for B cell ontogeny and integrates transcriptional and post-translational determinants of progression through the cell cycle.

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Posted November 12, 2019.
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Polypyrimidine Tract Binding Proteins are essential for B cell development
Elisa Monzón-Casanova, Louise S. Matheson, Kristina Tabbada, Kathi Zarnack, Christopher W. J. Smith, Martin Turner
bioRxiv 769141; doi: https://doi.org/10.1101/769141
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Polypyrimidine Tract Binding Proteins are essential for B cell development
Elisa Monzón-Casanova, Louise S. Matheson, Kristina Tabbada, Kathi Zarnack, Christopher W. J. Smith, Martin Turner
bioRxiv 769141; doi: https://doi.org/10.1101/769141

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