Effects of tRNA modification on translational accuracy depend on intrinsic codon-anticodon strength.
Effects of tRNA modification on translational accuracy depend on intrinsic codon-anticodon strength.
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DOI：
10.1093/nar/gkv1506
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发表时间：
2016-02-29
影响因子：
14.9
通讯作者：
Farabaugh PJ
中科院分区：
文献类型：
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作者：
Manickam N;Joshi K;Bhatt MJ;Farabaugh PJ
细胞的健康和生长要求蛋白质合成既要高效以确保足够的产量，又要准确以避免产生有缺陷或不稳定的蛋白质。单个 tRNA 误读错误频率的背景低至每个密码子 2 × 10−6，但具有密码子特异性，某些错误频率高于每个密码子 10−3。在这里，我们测试了阻断大肠杆菌中四种 tRNA 反密码子环的转录后修饰对错误频率的影响。我们发现对删除修改有两种类型的反应。阻止修改并增加错误，这表明修改至少在一定程度上起到了保持准确性的作用。阻止甚至相同的修改也会产生减少错误的相反效果。一种解释可能是，这些修饰在调节两类 tRNA 的误读方面发挥着相反的作用。然而，鉴于现有证据表明修饰有助于对反密码子进行预排序，使其能够识别密码子，然而，更简单的解释是，未经修饰的“弱”tRNA 解码效率太低，无法与通常解码目标密码子的同源 tRNA 竞争，这会降低误读的频率。
Cellular health and growth requires protein synthesis to be both efficient to ensure sufficient production, and accurate to avoid producing defective or unstable proteins. The background of misreading error frequency by individual tRNAs is as low as 2 × 10−6 per codon but is codon-specific with some error frequencies above 10−3 per codon. Here we test the effect on error frequency of blocking post-transcriptional modifications of the anticodon loops of four tRNAs in Escherichia coli. We find two types of responses to removing modification. Blocking modification of and increases errors, suggesting that the modifications act at least in part to maintain accuracy. Blocking even identical modifications of and has the opposite effect of decreasing errors. One explanation could be that the modifications play opposite roles in modulating misreading by the two classes of tRNAs. Given available evidence that modifications help preorder the anticodon to allow it to recognize the codons, however, the simpler explanation is that unmodified ‘weak’ tRNAs decode too inefficiently to compete against cognate tRNAs that normally decode target codons, which would reduce the frequency of misreading.