Lost in Translation: Defects in Transfer RNA Modifications and Neurological Disorders.
Lost in Translation: Defects in Transfer RNA Modifications and Neurological Disorders.
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DOI：
10.3389/fnmol.2017.00135
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发表时间：
2017
影响因子：
4.8
通讯作者：
Krishnan N
中科院分区：
文献类型：
--
作者：
Bednářová A;Hanna M;Durham I;VanCleave T;England A;Chaudhuri A;Krishnan N
转运rna （tRNAs）是参与蛋白质合成的关键分子。为了增强它们的功能，它们经历了广泛的转录后修饰，因此，它们受到多个水平的调控，包括转录、转录加工、定位和核糖核苷基修饰。转录后酶催化的tRNA修饰发生在许多碱基和糖的位置，影响特异性的反密码子-密码子相互作用，并调节翻译，其效率和保真度。这种核苷修饰现象最为显著，并导致tRNA具有丰富的结构多样性，其中已有100多种修饰的核苷被表征。这些超修饰核苷通常位于trna的摆动位置，它们在密码子识别以及维持翻译效率和保真度等方面发挥直接作用。最近的几项研究指出，tRNA修饰缺陷与包括神经系统疾病在内的人类疾病之间存在联系。因此，人类tRNA修饰的缺陷需要在酶和机制水平上进行深入的表征，以便为理解缺乏这种修饰如何与神经系统疾病相关铺平道路，最终目标是深入了解治疗干预措施。
Transfer RNAs (tRNAs) are key molecules participating in protein synthesis. To augment their functionality they undergo extensive post-transcriptional modifications and, as such, are subject to regulation at multiple levels including transcription, transcript processing, localization and ribonucleoside base modification. Post-transcriptional enzyme-catalyzed modification of tRNA occurs at a number of base and sugar positions and influences specific anticodon–codon interactions and regulates translation, its efficiency and fidelity. This phenomenon of nucleoside modification is most remarkable and results in a rich structural diversity of tRNA of which over 100 modified nucleosides have been characterized. Most often these hypermodified nucleosides are found in the wobble position of tRNAs, where they play a direct role in codon recognition as well as in maintaining translational efficiency and fidelity, etc. Several recent studies have pointed to a link between defects in tRNA modifications and human diseases including neurological disorders. Therefore, defects in tRNA modifications in humans need intensive characterization at the enzymatic and mechanistic level in order to pave the way to understand how lack of such modifications are associated with neurological disorders with the ultimate goal of gaining insights into therapeutic interventions.