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蛋白质合成过程中遗传密码误读的问题。

The problem of genetic code misreading during protein synthesis.

作者信息

Joshi Kartikeya, Cao Ling, Farabaugh Philip J

机构信息

Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, Maryland, USA.

出版信息

Yeast. 2019 Jan;36(1):35-42. doi: 10.1002/yea.3374.

DOI:10.1002/yea.3374
PMID:30557461
Abstract

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 × 10 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.

摘要

酿酒酵母一直是确定翻译错读事件频率的重要模型,翻译错读事件是指转运RNA(tRNA)与信使核糖核酸(mRNA)错误配对,并在mRNA中插入密码子未指定的氨基酸的情况。错读错误已在体内使用报告蛋白系统或质谱法进行了量化,两种方法都汇聚于一个关于大多数错读的简单模型。现有数据表明,错读的tRNA必须形成典型的碱基错配,这些错配与在核糖体A位点形成时可模拟沃森-克里克碱基对的错配相对应。涉及其他错配的错误发生频率要低得多。这项工作推翻了每个密码子平均错读频率为5×10的观点,该观点适用于整个遗传密码。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。对酿酒酵母和大肠杆菌中错读错误的比较表明,存在一种降低酵母中错读频率的机制;这种机制可能普遍存在于真核生物中。

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