Polypyrimidine Tract Binding Proteins are essential for B cell development

2019 ◽  
Author(s):  
Jonny Coates
2020 ◽  
Author(s):  
Elisa Monzón-Casanova ◽  
Louise S Matheson ◽  
Kristina Tabbada ◽  
Kathi Zarnack ◽  
Christopher WJ Smith ◽  
...  

2019 ◽  
Author(s):  
Elisa Monzón-Casanova ◽  
Louise S. Matheson ◽  
Kristina Tabbada ◽  
Kathi Zarnack ◽  
Christopher W. J. Smith ◽  
...  

AbstractPolypyrimidine 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.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Elisa Monzón-Casanova ◽  
Louise S Matheson ◽  
Kristina Tabbada ◽  
Kathi Zarnack ◽  
Christopher WJ Smith ◽  
...  

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.


Biochemistry ◽  
2018 ◽  
Vol 57 (26) ◽  
pp. 3873-3882 ◽  
Author(s):  
Jeffrey M. Pina ◽  
Janice M. Reynaga ◽  
Anthony A. M. Truong ◽  
Niroshika M. Keppetipola

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