同义密码子通过精微翻译选择机制实现对基因的表达调控

Regulation of fine-tuning translation selection mediated by synonymous codon usage for gene expression

摘要:

自然界中，同义密码子的存在使得众多氨基酸能够同时被多种密码子编码合成。随着研究的深入，同义密码子使用偏嗜性发挥出的生物学功能已经渗透到了基因复制、转录、翻译以及化学修饰等生命活动过程中。基于同义密码子使用偏嗜性的生物学特性，陆续发现密码子对(codon pair)和密码子共现(codon co-occurrence)同样在使用模式上存在明显的偏嗜性。在基因表达的过程中，针对编码序列的密码子优化能够显著提升基因的表达水平，这在生物工程领域对于蛋白表达有着重要的生物学意义。此外，同义密码子使用模式在调控基因转录、化学修饰以及翻译过程中间接控制着细胞内生命活动的有序性。而这些与同义密码子使用模式有着千丝万缕联系的生命过程主要是受精微翻译选择压力来调控运行的。本文中，我们结合当前同义密码子使用模式介导的精微翻译选择压力，简述密码子使用模式如何从转录、化学修饰以及翻译等方面来影响基因表达及蛋白产物生物学功能。这将为今后生物工程学领域如何优化蛋白高效表达以及深入研究重要生物学活动中基因表达调控提供可参考的思路与理念。

Abstract:

In nature,most amino acids are encoded by more than one codon which is termed as synonymous codon.Along with the deep investigations,synonymous codon usage bias is considered as one important factor in gene replication,transcription,translation and modification.According to the biological functions of synonymous codon usage bias,the biased usage patterns have been verified in codon pair and codon co-occurrence as well.In gene expression,codon optimization can assist the gene of interest in enhancing its translational efficiency,which benefits the field of biological engineering in terms of protein expression.Moreover,synonymous codon usage pattern indirectly mediates biological processes related to transcription,chemical modification and translation in cells.The performances involved in the important life cycles mentioned above can be carried out by fine-tuning translation selection derived from synonymous codon usage bias.In this review,we tried to clarify how fine-tuning translation selection participated in gene expression and protein function via transcription,chemical modification and translation,and provide some new insights into optimal gene expression and the mechanism underlying the regulation of gene expression.