Abstract

The genetic code sets the correspondence between the sequence of a given nucleotide triplet in an mRNA molecule, called a codon, and the amino acid that is added to the growing polypeptide chain during protein synthesis. With four bases (A, G, U, and C), there are 64 possible triplet codons: 61 sense codons (encoding amino acids) and 3 nonsense codons (so-called, stop codons that define termination of translation). In most organisms, there are 20 common/standard amino acids used in protein synthesis; thus, the genetic code is redundant with most amino acids (with the exception of Met and Trp) are being encoded by more than one (synonymous) codon. Synonymous codons were initially presumed to have entirely equivalent functions, however, the finding that synonymous codons are not present at equal frequencies in mRNA suggested that the specific codon choice might have functional implications beyond coding for amino acid. Observation of nonequivalent use of codons in mRNAs implied a possibility of the existence of auxiliary information in the genetic code. Indeed, it has been found that genetic code contains several layers of such additional information and that synonymous codons are strategically placed within mRNAs to ensure a particular translation kinetics facilitating and fine-tuning co-translational protein folding in the cell via step-wise/sequential structuring of distinct regions of the polypeptide chain emerging from the ribosome at different points in time. This review summarizes key findings in the field that have identified the role of synonymous codons and their usage in protein folding in the cell.

中文翻译：

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代码中的代码：密码子如何微调细胞中的蛋白质折叠

摘要

遗传密码设定了 mRNA 分子中给定核苷酸三联体的序列（称为密码子）与蛋白质合成过程中添加到不断增长的多肽链的氨基酸之间的对应关系。有四个碱基（A、G、U 和 C），有 64 个可能的三联密码子：61 个有义密码子（编码氨基酸）和 3 个无义密码子（所谓的定义翻译终止的终止密码子）。在大多数生物体中，有 20 种常见/标准氨基酸用于蛋白质合成；因此，遗传密码是多余的，大多数氨基酸（Met 和 Trp 除外）由多个（同义）密码子编码。最初假定同义密码子具有完全相同的功能，然而，同义密码子在 mRNA 中不以相同频率存在的发现表明，特定密码子的选择可能具有超出编码氨基酸的功能意义。观察到 mRNA 中密码子的非等效使用暗示了遗传密码中存在辅助信息的可能性。事实上，已经发现遗传密码包含多层这样的附加信息，并且同义密码子被战略性地放置在 mRNA 中以确保特定的翻译动力学通过逐步/顺序促进和微调细胞中的共翻译蛋白质折叠不同时间点从核糖体中出现的多肽链不同区域的结构。