Polypyrimidine tract-binding proteins are essential for B cell development

Elife. 2020 Feb 21;9:e53557. doi: 10.7554/eLife.53557.

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.

Keywords: B cell development; RNA-binding proteins; alternative splicing; cell cycle; chromosomes; gene expression; immunology; inflammation; mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism*
  • Cell Cycle
  • Cell Differentiation
  • Cell Proliferation
  • Female
  • Flow Cytometry
  • Gene Expression Regulation
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism
  • Heterogeneous-Nuclear Ribonucleoproteins / physiology*
  • Male
  • Mice
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology
  • Polypyrimidine Tract-Binding Protein / metabolism
  • Polypyrimidine Tract-Binding Protein / physiology*
  • RNA-Binding Proteins / metabolism
  • RNA-Binding Proteins / physiology

Substances

  • Heterogeneous-Nuclear Ribonucleoproteins
  • Nerve Tissue Proteins
  • Ptbp1 protein, mouse
  • Ptbp2 protein, mouse
  • RNA-Binding Proteins
  • Polypyrimidine Tract-Binding Protein

Associated data

  • GEO/GSE136882
  • GEO/GSM1520118
  • GEO/GSM1520115
  • GEO/GSM1520116
  • GEO/GSM1520117
  • GEO/GSE62129