Tia1 dependent regulation of mRNA subcellular location and translation controls p53 expression in B cells.
Tia1 dependent regulation of mRNA subcellular location and translation controls p53 expression in B cells.
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DOI：
10.1038/s41467-017-00454-2
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发表时间：
2017-09-13
影响因子：
16.6
通讯作者：
Turner M
中科院分区：
文献类型：
--
作者：
Díaz-Muñoz MD;Kiselev VY;Le Novère N;Curk T;Ule J;Turner M
转录后调控是蛋白质合成所必需的。在这里，我们描述了在B淋巴细胞激活和DNA损伤反应过程中，mRNA翻译抑制和mRNA亚细胞定位对蛋白质表达的重要性。细胞质RNA颗粒是在细胞与有丝分裂原激活时形成的，包括含有RNA结合蛋白Tia1的应激颗粒。Tia1与细胞应激相关的转录子结合，包括P53 mRNA，控制翻译沉默和RNA颗粒定位。DNA损伤促进了信使核糖核酸的重新定位和翻译，部分原因是Tia1与其信使核糖核酸靶标解离。DNA损伤后，应激颗粒释放P53 mRNA，并与多聚核糖体结合，以不依赖于CAP的方式增加蛋白质合成。对细胞mRNA丰度和翻译的全局分析表明，这是一种扩展的ATM依赖机制，以增加DNA损伤反应的关键调节因子的蛋白质表达。在细胞质应激颗粒中隔离mRNA是翻译抑制的一种机制。在这里，作者发现，存在于激活的B淋巴细胞的应激颗粒中的P53 mRNA在DNA损伤时被释放，并以不依赖于CAP的方式翻译。
Post-transcriptional regulation of cellular mRNA is essential for protein synthesis. Here we describe the importance of mRNA translational repression and mRNA subcellular location for protein expression during B lymphocyte activation and the DNA damage response. Cytoplasmic RNA granules are formed upon cell activation with mitogens, including stress granules that contain the RNA binding protein Tia1. Tia1 binds to a subset of transcripts involved in cell stress, including p53 mRNA, and controls translational silencing and RNA granule localization. DNA damage promotes mRNA relocation and translation in part due to dissociation of Tia1 from its mRNA targets. Upon DNA damage, p53 mRNA is released from stress granules and associates with polyribosomes to increase protein synthesis in a CAP-independent manner. Global analysis of cellular mRNA abundance and translation indicates that this is an extended ATM-dependent mechanism to increase protein expression of key modulators of the DNA damage response. Sequestering mRNA in cytoplasmic stress granules is a mechanism for translational repression. Here the authors find that p53 mRNA, present in stress granules in activated B lymphocytes, is released upon DNA damage and is translated in a CAP-independent manner.
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影响因子：
56.9
作者：
Allen, Christopher D. C.;Okada, Takaharu;Cyster, Jason G.
通讯作者：
Cyster, Jason G.
DOI：
10.1101/sqb.2000.65.395
发表时间：
2000-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
Ferguson, DO;Sekiguchi, JM;Alt, FW
通讯作者：
Alt, FW
影响因子：
4.1
作者：
Grover, Richa;Sharathchandra, Arandkar;Das, Saumitra
通讯作者：
Das, Saumitra
影响因子：
64.5
作者：
ELDEIRY, WS;TOKINO, T;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
DOI：
10.4049/jimmunol.181.4.2620
发表时间：
2008-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Bredemeyer AL;Huang CY;Walker LM;Bassing CH;Sleckman BP
通讯作者：
Sleckman BP