Protein synthesis on the ribosome involves successive rapid recruitment of cognate aminoacyl-tRNAs and rejection of the much more numerous incorrect near- or non-cognates. The principal feature of translation elongation is that at every step, many incorrect aa-tRNAs unsuccessfully enter the A site for each cognate accepted. Normal levels of translational accuracy require that cognate tRNAs have relatively similar acceptance rates by the ribosome. To achieve that, tRNAs evolved to compensate for differences in amino acid properties and codon–anticodon strength that affect acceptance. Part of that response involved tRNA posttranscriptional modifications, which can affect tRNA decoding efficiency, accuracy, and structural stability. The most intensively modified regions of the tRNA are the anticodon loop and structural core of the tRNA. Anticodon loop modifications directly affect codon–anticodon pairing and therefore modulate accuracy. Core modifications have been thought to ensure consistent decoding rates principally by stabilizing tRNA structure to avoid degradation; however, degradation due to instability appears to only be a significant issue above normal growth temperatures. We suspected that the greater role of modification at normal temperatures might be to tune tRNAs to maintain consistent intrinsic rates of acceptance and peptide transfer and that hypomodification by altering these rates might degrade the process of discrimination, leading to increased translational errors. Here, we present evidence that most tRNA core modifications do modulate the frequency of misreading errors, suggesting that the need to maintain accuracy explains their deep evolutionary conservation.

中文翻译：

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tRNA 核心的转录后修饰可调节翻译误读错误

核糖体上的蛋白质合成涉及同源氨酰基-tRNA 的连续快速募集和大量不正确的近源或非同源的排斥。翻译延伸的主要特征是，在每一步中，许多不正确的 aa-tRNA 未能成功进入每个接受的同源的 A 位点。正常水平的翻译准确性要求同源 tRNA 具有相对相似的核糖体接受率。为了实现这一目标，tRNA 不断进化以补偿影响接受度的氨基酸特性和密码子-反密码子强度的差异。该反应的一部分涉及 tRNA 转录后修饰，这会影响 tRNA 解码效率、准确性和结构稳定性。 tRNA 修饰最密集的区域是 tRNA 的反密码子环和结构核心。反密码子环修饰直接影响密码子-反密码子配对，从而调节准确性。核心修饰被认为主要通过稳定 tRNA 结构以避免降解来确保一致的解码率；然而，由于不稳定性导致的降解似乎只是高于正常生长温度的一个重大问题。我们怀疑，常温下修饰的更大作用可能是调整 tRNA，以保持一致的内在接受率和肽转移，而通过改变这些速率进行的低修饰可能会降低辨别过程，导致翻译错误增加。在这里，我们提供的证据表明，大多数 tRNA 核心修饰确实会调节误读错误的频率，这表明保持准确性的需要解释了它们的深层进化保守性。