Chevance Fabienne F V, Hughes Kelly T
Department of Biology, University of Utah, Salt Lake City, UT 84112.
Department of Biology, University of Utah, Salt Lake City, UT 84112
Proc Natl Acad Sci U S A. 2017 May 2;114(18):4745-4750. doi: 10.1073/pnas.1614896114. Epub 2017 Apr 17.
The efficiency of codon translation in vivo is controlled by many factors, including codon context. At a site early in the gene, the effects on translation of replacing codons Thr6 and Pro8 of with synonymous alternates produced a 600-fold range in FlgM activity. Synonymous changes at Thr6 and Leu9 resulted in a twofold range in FlgM activity. The level of FlgM activity produced by any codon arrangement was directly proportional to the degree of in vivo ribosome stalling at synonymous codons. Synonymous codon suppressors that corrected the effect of a translation-defective synonymous allele were restricted to two codons flanking the translation-defective codon. The various codon arrangements had no apparent effects on mRNA stability or predicted mRNA secondary structures. Our data suggest that efficient mRNA translation is determined by a triplet-of-triplet genetic code. That is, the efficiency of translating a particular codon is influenced by the nature of the immediately adjacent flanking codons. A model explains these codon-context effects by suggesting that codon recognition by elongation factor-bound aminoacyl-tRNA is initiated by hydrogen bond interactions between the first two nucleotides of the codon and anticodon and then is stabilized by base-stacking energy over three successive codons.
体内密码子翻译的效率受多种因素控制，包括密码子上下文。在基因早期的一个位点，用同义替代物替换苏氨酸6（Thr6）和脯氨酸8（Pro8）密码子对翻译的影响使FlgM活性产生了600倍的变化范围。苏氨酸6（Thr6）和亮氨酸9（Leu9）的同义变化导致FlgM活性有两倍的变化范围。任何密码子排列产生的FlgM活性水平与体内同义密码子处核糖体停滞的程度直接相关。校正翻译缺陷同义等位基因效应的同义密码子抑制子仅限于翻译缺陷密码子两侧的两个密码子。各种密码子排列对mRNA稳定性或预测的mRNA二级结构没有明显影响。我们的数据表明，有效的mRNA翻译由三联体对三联体遗传密码决定。也就是说，翻译特定密码子的效率受紧邻侧翼密码子性质的影响。一个模型通过表明延伸因子结合的氨酰tRNA对密码子的识别由密码子和反密码子前两个核苷酸之间的氢键相互作用启动，然后通过三个连续密码子上的碱基堆积能量稳定，来解释这些密码子上下文效应。
