密码子中的密码:密码子偏好性与基因表达的精细调控

Codon codes:Codon usage bias influences many levels of gene expression

同义突变由于不改变编码蛋白质的氨基酸序列,常被认为是"沉默"突变.实际上,同义密码子的选择在进化尺度上是受到限制的,从而致使同义密码子的使用频率存在差异,称为密码子偏好性.密码子偏好性在转录、转录后加工、mRNA稳定性、翻译起始、延伸、蛋白折叠等方面都起着精细调节的作用.因此,同义突变在很多情况下可导致癌症等各类疾病的发生.本综述在分子机制层面简述了近年来关于密码子偏好性对翻译和转录过程调节作用的进展,以及对于基础研究及医学方面的意义.

Synonymous mutations, which do not change the primary sequences of encoded proteins, are often recognized as silent mutations. In particular, the selection of synonymous codons at an evolutionary scale is constrained and has resulted in uneven occurrences, a phenomenon called codon usage bias. In recent decades, the roles of codon usage bias in fine-tuning transcription, post-transcriptional processing, mRNA stability, translation initiation, elongation, and peptide folding have been revealed. Upon disrupting these biological processes, synonymous mutations have been reported to cause various diseases such as cancer. Herein, we briefly review the current understanding concerning the molecular mechanisms of transcription and translation processes regulated by codon usage bias as well as the implications for basic and translational research inmedicine.