First Author | Monzón-Casanova E | Year | 2020 |
Journal | Elife | Volume | 9 |
PubMed ID | 32081131 | Mgi Jnum | J:306203 |
Mgi Id | MGI:6706134 | Doi | 10.7554/eLife.53557 |
Citation | Monzon-Casanova E, et al. (2020) Polypyrimidine tract-binding proteins are essential for B cell development. Elife 9:e53557 |
abstractText | 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. |