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

Authors
  • Monzón-Casanova, Elisa
  • Matheson, Louise S
  • Tabbada, Kristina
  • Zarnack, Kathi
  • Smith, Christopher Wj
  • Turner, Martin
Publication Date
Feb 21, 2020
Source
Apollo - University of Cambridge Repository
Keywords
Language
English
License
Green
External links

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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