The Importance of Being Modified: The Role of RNA Modifications in Translational Fidelity.
The Importance of Being Modified: The Role of RNA Modifications in Translational Fidelity.
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DOI：
10.1016/bs.enz.2017.03.005
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Eruysal E
中科院分区：
文献类型：
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作者：
Agris PF;Narendran A;Sarachan K;Väre VYP;Eruysal E
tRNA的反密码子茎环（ASL）结构域的转录后修饰代表了将mRNA密码子翻译成蛋白质的正确氨基酸序列的准确性和效率的第三水平，第三密码。tRNA的ASL结构域的修饰是酶促合成的，并且位点特异性地位于反密码子摆动位置-34和3 '-邻近位置-37处的反密码子。64个通用遗传密码的简并性和tRNA种类数量的限制要求一些tRNA解码多于一个密码子。特定的修饰化学及其对tRNA的ASL结构和动力学的影响使一种tRNA能够解码同源和“摆动密码子”或将识别扩展到同义密码子，同时保持翻译阅读框架。一些修饰的核苷的化学物质预构tRNA以读取共享双重简并密码子盒的特定氨基酸的两个密码子，而其他化学物质允许不同的tRNA响应四重简并密码子盒的所有四个密码子。因此，tRNA ASL修饰是关键的，并且修饰酶和tRNA的基因突变（其结果是缺乏修饰）导致误译和人类疾病。通过优化所有生物体中tRNA反密码子的化学、结构和动力学，修饰确保mRNA转录物的翻译保真度。
The posttranscriptional modifications of tRNA's anticodon stem and loop (ASL) domain represent a third level, a third code, to the accuracy and efficiency of translating mRNA codons into the correct amino acid sequence of proteins. Modifications of tRNA's ASL domain are enzymatically synthesized and site specifically located at the anticodon wobble position-34 and 3′-adjacent to the anticodon at position-37. Degeneracy of the 64 Universal Genetic Codes and the limitation in the number of tRNA species require some tRNAs to decode more than one codon. The specific modification chemistries and their impact on the tRNA's ASL structure and dynamics enable one tRNA to decode cognate and “wobble codons” or to expand recognition to synonymous codons, all the while maintaining the translational reading frame. Some modified nucleosides’ chemistries prestructure tRNA to read the two codons of a specific amino acid that shares a twofold degenerate codon box, and other chemistries allow a different tRNA to respond to all four codons of a fourfold degenerate codon box. Thus, tRNA ASL modifications are critical and mutations in genes for the modification enzymes and tRNA, the consequences of which is a lack of modification, lead to mistranslation and human disease. By optimizing tRNA anticodon chemistries, structure, and dynamics in all organisms, modifications ensure translational fidelity of mRNA transcripts.