Polypyrimidine tract-binding proteins are essential for B cell development.

Change log
Monzón-Casanova, Elisa  ORCID logo  https://orcid.org/0000-0001-6617-6138
Matheson, Louise S 
Tabbada, Kristina 
Smith, Christopher Wj  ORCID logo  https://orcid.org/0000-0002-2753-3398

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
Journal Title
Conference Name
Journal ISSN
Volume Title
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)