Polypyrimidine Tract Binding Proteins are essential for B cell development
Polypyrimidine Tract Binding Proteins are essential for B cell development
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多聚嘧啶束结合蛋白对于 B 细胞发育至关重要
DOI：
10.1101/769141
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Monzón-Casanova E
中科院分区：
文献类型：
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作者：
Monzón-Casanova E
多聚嘧啶片段结合蛋白1（PTBP 1）是在整个B细胞发育过程中表达的RNA结合蛋白（RBP）。小鼠前B细胞中Ptbp 1的缺失导致PTBP 2的上调和正常B细胞发育。我们发现PTBP 2在B细胞个体发育中补偿PTBP 1，因为Ptbp 1和Ptbp 2的缺失导致前B细胞阶段的完全阻断和成熟B细胞的缺乏。在pro-B细胞中，PTBP 1确保细胞周期蛋白依赖性激酶在细胞周期不同阶段的活性精确同步，抑制S期进入并促进有丝分裂的进展。PTBP 1控制mRNA丰度和重要细胞周期调节因子的选择性剪接，包括CYP 1D 2、c-MYC、p107和CDC 25 B。我们的研究结果揭示了一个以前未被认识的机制，介导的RBP是必不可少的B细胞个体发育和整合的转录和翻译后决定因素的进展，通过细胞周期。
Polypyrimidine tract-binding protein 1 (PTBP1) is a RNA-binding protein (RBP) expressed throughout B cell development. Deletion ofPtbp1in 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 bothPtbp1andPtbp2results 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.