The problem of genetic code misreading during protein synthesis
The problem of genetic code misreading during protein synthesis
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DOI：
10.1002/yea.3374
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发表时间：
2019-01-01
期刊：
影响因子：
2.6
通讯作者：
Farabaugh, Philip J.
中科院分区：
文献类型：
--
作者：
Joshi, Kartikeya;Cao, Ling;Farabaugh, Philip J.
酿酒酵母一直是确定翻译误读事件频率的重要模型，在这些事件中，tRNA与mRNA不正确配对，并在mRNA中插入密码子未指定的氨基酸。误读错误已在体内定量报告蛋白质系统或质谱，这两种方法收敛于一个简单的模型，大多数误读。现有的数据表明，误读的tRNA必须形成刻板的碱基错配，对应于那些可以模仿沃森-克里克碱基对时，在核糖体A位点形成。涉及其他不匹配的错误发生的频率要低得多。这项工作揭穿了平均误读频率为5 × 10（-4）每个密码子的想法，该密码子延伸到整个遗传密码。相反，错误分为两个不同的类别-高频和低频事件-大多数错误属于低频类型。对S.酿酒酵母和大肠杆菌的研究表明，存在一种机制，减少酵母中的误读频率;这种机制可能在真核生物中普遍运作。
Saccharomyces cerevisiae has been an important model for determining the frequency of translational misreading events, those in which a tRNA pairs incorrectly to the mRNA and inserts an amino acid not specified by the codon in the mRNA. Misreading errors have been quantified in vivo using reporter protein systems or mass spectrometry with both approaches converging on a simple model for most misreading. The available data show that misreading tRNAs must form stereotypical base mismatches that correspond to those that can mimic Watson-Crick base pairs when formed in the ribosomal A site. Errors involving other mismatches occur significantly less frequently. This work debunks the idea of an average misreading frequency of 5 x 10(-4) per codon that extends across the genetic code. Instead, errors come in two distinct classes-high frequency and low frequency events-with most errors being of the low frequency type. A comparison of misreading errors in S. cerevisiae and Escherichia coli suggests the existence of a mechanism that reduces misreading frequency in yeast; this mechanism may operate in eukaryotes generally.