RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence
RNA-binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence
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DOI：
10.1126/science.aad5978
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发表时间：
2016-04-22
期刊：
影响因子：
56.9
通讯作者：
Turner, Martin
中科院分区：
文献类型：
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作者：
Galloway, Alison;Saveliev, Alexander;Turner, Martin
淋巴细胞发育各阶段的进展需要细胞周期的协调。这种协调确保了基因组的完整性，同时细胞系统地重排其抗原受体基因[在一个称为可变多样性连接(VDJ)重组的过程中]，并在成功重排后扩大祖细胞淋巴细胞库。在此，我们发现在B淋巴细胞发育过程中，RNA结合蛋白(RBP)Zfp36L1和Zfp36L2对于维持前体B细胞受体(Pre-BCR)表达前的静止状态以及在Pre-BCR诱导的扩增后重新建立静止状态至关重要。这些限制性商业惯例抑制了由信使RNA组成的进化保守的转录后调控子，信使RNA的蛋白质产物协同促进进入细胞周期的S阶段。这一机制促进了VDJ的重组和在BCR前检查点表达免疫球蛋白-m的细胞的有效选择。
Progression through the stages of lymphocyte development requires coordination of the cell cycle. Such coordination ensures genomic integrity while cells somatically rearrange their antigen receptor genes [in a process called variable-diversity-joining (VDJ) recombination] and, upon successful rearrangement, expands the pools of progenitor lymphocytes. Here we show that in developing B lymphocytes, the RNA-binding proteins (RBPs) ZFP36L1 and ZFP36L2 are critical for maintaining quiescence before precursor B cell receptor (pre-BCR) expression and for reestablishing quiescence after pre-BCR-induced expansion. These RBPs suppress an evolutionarily conserved post-transcriptional regulon consisting of messenger RNAs whose protein products cooperatively promote transition into the S phase of the cell cycle. This mechanism promotes VDJ recombination and effective selection of cells expressing immunoglobulin-m at the pre-BCR checkpoint.