Polypyrimidine tract binding proteins are essential for B cell development

Polypyrimidine Tract Binding Protein 1 (PTBP1) is a RNA-binding protein (RBP) expressed throughout B cell development. Deletion ofPtbp1 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 bothPtbp1 andPtbp2 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.
Source: eLife - Category: Biomedical Science Tags: Chromosomes and Gene Expression Immunology and Inflammation Source Type: research

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