A Code Within a Code: How Codons Fine-Tune Protein Folding in the Cell.
A Code Within a Code: How Codons Fine-Tune Protein Folding in the Cell.
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DOI：
10.1134/s0006297921080083
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发表时间：
2021-08
期刊：
影响因子：
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通讯作者：
Komar AA
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作者：
Komar AA
遗传密码设置了信使核糖核酸分子中给定的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中的氨基酸之间的对应关系。有四个碱基(A、G、U、C)，可能有三重密码子：61个有义密码子(编码氨基酸)和3个无义密码子(即定义翻译终止的所谓终止密码子)。在大多数生物中，有20种常见的/标准的氨基酸用于蛋白质合成；因此，遗传密码是多余的，因为大多数氨基酸(Met和Trp除外)由一个以上(同义的)密码子编码。同义密码子最初被认为具有完全相同的功能，然而，发现同义密码子在mRNA中出现的频率不同，这表明特定的密码子选择可能具有除编码氨基酸以外的功能含义。观察到mRNAs中密码子的不同用法暗示了遗传密码中存在辅助信息的可能性。事实上，人们已经发现，遗传密码包含几层这样的额外信息，同义密码子被策略性地放置在mRNAs中，以确保特定的翻译动力学，通过逐步/顺序地构建在不同时间点从核糖体出现的多肽链的不同区域，促进和微调细胞中的共翻译蛋白质折叠。这篇综述总结了该领域的关键发现，这些发现已经确定了同义密码子的作用及其在细胞中蛋白质折叠中的用途。
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.