Polypyrimidine tract-binding proteins are essential for B cell development.
Matheson, Louise S
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Monzón-Casanova, E., Matheson, L. S., Tabbada, K., Zarnack, K., Smith, C. W., & Turner, M. (2020). Polypyrimidine tract-binding proteins are essential for B cell development.. eLife, 9 https://doi.org/10.7554/eLife.53557
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.
Cell cycle, Mouse, Alternative splicing, Inflammation, chromosomes, immunology, Gene Expression, RNA-binding proteins, B Cell Development
European Cooperation in Science and Technology (CA17103)
Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0427, BBS/E/B/000C0428, BB/J00152X/1, BB/P01898X/1, BBS/E/B/000C0407)
German Research Foundation (ZA 881/2-1)
Wellcome Trust (200823/Z/16/Z)
External DOI: https://doi.org/10.7554/eLife.53557
This record's URL: https://www.repository.cam.ac.uk/handle/1810/303758
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/