A system of RNA modifications and biased codon use controls cellular stress response at the level of translation.
A system of RNA modifications and biased codon use controls cellular stress response at the level of translation.
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DOI：
10.1021/tx400438d
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发表时间：
2014-03-17
影响因子：
4.1
通讯作者：
Begley, Thomas J.
中科院分区：
文献类型：
--
作者：
Dedon, Peter C.;Begley, Thomas J.
细胞对环境应激源和外源性暴露的反应使用调控网络来控制基因表达，并且对DNA、RNA和蛋白质的许多合成后化学修饰在控制应激反应的转录和翻译中的作用有了新的认识。在这个角度来看，我们提出了一个新的网络模型，调节细胞对外源性暴露和其他压力的反应，其中压力诱导的重编程系统的几十个转录后修饰的tRNA（tRNA）促进关键反应蛋白的密码子偏向mRNA的选择性翻译。作为新的基因组和生物分析技术的产物，该模型与表观遗传学中的DNA甲基化调控网络以及包括信号通路和组蛋白密码的各种蛋白质二级修饰具有很强的相似性。当存在于tRNA摆动位置时，修饰的核糖核苷增强mRNA的翻译，其中tRNA的同源密码子高度过量表达并且代表关键的应激反应蛋白。平行系统也可以下调蛋白质家族的翻译。值得注意的是，人类中tRNA甲基转移酶的失调也与癌症病因学有关，具有已证实的致癌和肿瘤抑制作用。
Cells respond to environmental stressors and xenobiotic exposures using regulatory networks to control gene expression, and there is an emerging appreciation for the role of numerous postsynthetic chemical modifications of DNA, RNA, and proteins in controlling transcription and translation of the stress response. In this Perspective, we present a model for a new network that regulates the cellular response to xenobiotic exposures and other stresses in which stress-induced reprogramming of a system of dozens of post-transcriptional modifications on tRNA (tRNA) promotes selective translation of codon-biased mRNAs for critical response proteins. As a product of novel genomic and bioanalytical technologies, this model has strong parallels with the regulatory networks of DNA methylation in epigenetics and the variety of protein secondary modifications comprising signaling pathways and the histone code. When present at the tRNA wobble position, the modified ribonucleosides enhance the translation of mRNAs in which the cognate codons of the tRNAs are highly over-represented and that represent critical stress response proteins. A parallel system may also downregulate the translation of families of proteins. Notably, dysregulation of the tRNA methyltransferase enzymes in humans has also been implicated in cancer etiology, with demonstrated oncogenic and tumor-suppressive effects.
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影响因子：
14.9
作者：
EMILSSON, V;NASLUND, AK;KURLAND, CG
通讯作者：
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影响因子：
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