Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom.
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
Elife. 2020 Feb 21;9:e53557. doi: 10.7554/eLife.53557.
Polypyrimidine tract-binding protein 1 (PTBP1) is a RNA-binding protein (RBP) expressed throughout B cell development. Deletion of 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 and 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.
多嘧啶 tract 结合蛋白 1 (PTBP1) 是一种在 B 细胞发育过程中表达的 RNA 结合蛋白 (RBP)。在小鼠前 B 细胞中缺失 会导致 PTBP2 的上调和正常 B 细胞的发育。我们表明，PTBP2 在 B 细胞发生中补偿了 PTBP1 的作用，因为缺失 和 都会导致前 B 细胞阶段完全阻断和成熟 B 细胞缺失。在前 B 细胞中，PTBP1 确保细胞周期中不同阶段的细胞周期依赖性激酶的活性精确同步，抑制 S 期进入并促进进入有丝分裂。PTBP1 控制重要细胞周期调节剂包括 CYCLIN-D2、c-MYC、p107 和 CDC25B 的 mRNA 丰度和选择性剪接。我们的结果揭示了一种以前未被识别的机制，该机制由一种对 B 细胞发生至关重要的 RBP 介导，并整合了转录和翻译后决定通过细胞周期的决定因素。
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