|
Codon-resolution Analysis Reveals a Direct and Context-dependent Impact of Individual Synonymous Mutations on mRNA Level
Siyu Chen, Ke Li, Wenqing Cao, Jia Wang, Tong Zhao, Qing Huan, Yu-Fei Yang, Shaohuan Wu and Wenfeng Qian
Molecular Biology and Evolution
Abstract
Codon usage bias (CUB) refers to the observation that synonymous codons are not used equally frequently in a genome. CUB is stronger in more highly expressed genes, a phenomenon commonly explained by stronger natural selection on translational accuracy and/or efficiency among these genes. Nevertheless, this phenomenon could also occur if CUB regulates gene expression at the mRNA level, a hypothesis that has not been tested until recently. Here, we attempt to quantify the impact of synonymous mutations on mRNA level in yeast using 3,556 synonymous variants of a heterologous gene encoding green fluorescent protein (GFP) and 523 synonymous variants of an endogenous gene TDH3. We found that mRNA level was positively correlated with CUB among these synonymous variants, demonstrating a direct role of CUB in regulating transcript concentration, likely via regulating mRNA degradation rate, as our additional experiments suggested. More importantly, we quantified the effects of individual synonymous mutations on mRNA level and found them dependent on (i) CUB and (ii) mRNA secondary structure, both in proximal sequence contexts. Our study reveals the pleiotropic effects of synonymous codon usage and provides an additional explanation for the well-known correlation between CUB and gene expression level.
|
论文编号: |
DOI:10.1093/molbev/msx229 |
论文题目: |
Codon-resolution Analysis Reveals a Direct and Context-dependent Impact of Individual Synonymous Mutations on mRNA Level |
英文论文题目: |
Codon-resolution Analysis Reveals a Direct and Context-dependent Impact of Individual Synonymous Mutations on mRNA Level |
第一作者: |
Siyu Chen, Ke Li, Wenqing Cao, Jia Wang, Tong Zhao, Qing Huan, Yu-Fei Yang, Shaohuan Wu and Wenfeng Qian |
英文第一作者: |
Siyu Chen, Ke Li, Wenqing Cao, Jia Wang, Tong Zhao, Qing Huan, Yu-Fei Yang, Shaohuan Wu and Wenfeng Qian |
联系作者: |
|
英文联系作者: |
|
外单位作者单位: |
|
英文外单位作者单位: |
|
发表年度: |
2017-08-28 |
卷: |
|
期: |
|
页码: |
|
摘要: |
Codon usage bias (CUB) refers to the observation that synonymous codons are not used equally frequently in a genome. CUB is stronger in more highly expressed genes, a phenomenon commonly explained by stronger natural selection on translational accuracy and/or efficiency among these genes. Nevertheless, this phenomenon could also occur if CUB regulates gene expression at the mRNA level, a hypothesis that has not been tested until recently. Here, we attempt to quantify the impact of synonymous mutations on mRNA level in yeast using 3,556 synonymous variants of a heterologous gene encoding green fluorescent protein (GFP) and 523 synonymous variants of an endogenous gene TDH3. We found that mRNA level was positively correlated with CUB among these synonymous variants, demonstrating a direct role of CUB in regulating transcript concentration, likely via regulating mRNA degradation rate, as our additional experiments suggested. More importantly, we quantified the effects of individual synonymous mutations on mRNA level and found them dependent on (i) CUB and (ii) mRNA secondary structure, both in proximal sequence contexts. Our study reveals the pleiotropic effects of synonymous codon usage and provides an additional explanation for the well-known correlation between CUB and gene expression level. |
英文摘要: |
Codon usage bias (CUB) refers to the observation that synonymous codons are not used equally frequently in a genome. CUB is stronger in more highly expressed genes, a phenomenon commonly explained by stronger natural selection on translational accuracy and/or efficiency among these genes. Nevertheless, this phenomenon could also occur if CUB regulates gene expression at the mRNA level, a hypothesis that has not been tested until recently. Here, we attempt to quantify the impact of synonymous mutations on mRNA level in yeast using 3,556 synonymous variants of a heterologous gene encoding green fluorescent protein (GFP) and 523 synonymous variants of an endogenous gene TDH3. We found that mRNA level was positively correlated with CUB among these synonymous variants, demonstrating a direct role of CUB in regulating transcript concentration, likely via regulating mRNA degradation rate, as our additional experiments suggested. More importantly, we quantified the effects of individual synonymous mutations on mRNA level and found them dependent on (i) CUB and (ii) mRNA secondary structure, both in proximal sequence contexts. Our study reveals the pleiotropic effects of synonymous codon usage and provides an additional explanation for the well-known correlation between CUB and gene expression level. |
刊物名称: |
Molecular Biology and Evolution |
英文刊物名称: |
Molecular Biology and Evolution |
论文全文: |
|
英文论文全文: |
|
全文链接: |
|
其它备注: |
Siyu Chen, Ke Li, Wenqing Cao, Jia Wang, Tong Zhao, Qing Huan, Yu-Fei Yang, Shaohuan Wu and Wenfeng Qian. Codon-resolution Analysis Reveals a Direct and Context-dependent Impact of Individual Synonymous Mutations on mRNA Level. Molecular Biology and Evolution. DOI:10.1093/molbev/msx229 |
英文其它备注: |
|
学科: |
|
英文学科: |
|
影响因子: |
|
第一作者所在部门: |
|
英文第一作者所在部门: |
|
论文出处: |
|
英文论文出处: |
|
论文类别: |
|
英文论文类别: |
|
参与作者: |
|
英文参与作者: |
|
|