当前位置: X-MOL 学术Nucleic Acids Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Codon usage and protein length-dependent feedback from translation elongation regulates translation initiation and elongation speed
Nucleic Acids Research ( IF 16.6 ) Pub Date : 2021-08-17 , DOI: 10.1093/nar/gkab729
Xueliang Lyu 1, 2 , Qian Yang 1 , Fangzhou Zhao 1 , Yi Liu 1
Affiliation  

Essential cellular functions require efficient production of many large proteins but synthesis of large proteins encounters many obstacles in cells. Translational control is mostly known to be regulated at the initiation step. Whether translation elongation process can feedback to regulate initiation efficiency is unclear. Codon usage bias, a universal feature of all genomes, plays an important role in determining gene expression levels. Here, we discovered that there is a conserved but codon usage-dependent genome-wide negative correlation between protein abundance and CDS length. The codon usage effects on protein expression and ribosome flux on mRNAs are influenced by CDS length; optimal codon usage preferentially promotes production of large proteins. Translation of mRNAs with long CDS and non-optimal codon usage preferentially induces phosphorylation of initiation factor eIF2α, which inhibits translation initiation efficiency. Deletion of the eIF2α kinase CPC-3 (GCN2 homolog) in Neurospora preferentially up-regulates large proteins encoded by non-optimal codons. Surprisingly, CPC-3 also inhibits translation elongation rate in a codon usage and CDS length-dependent manner, resulting in slow elongation rates for long CDS mRNAs. Together, these results revealed a codon usage and CDS length-dependent feedback mechanism from translation elongation to regulate both translation initiation and elongation kinetics.

中文翻译:

来自翻译延伸的密码子使用和蛋白质长度依赖性反馈调节翻译起始和延伸速度

基本的细胞功能需要有效生产许多大蛋白,但大蛋白的合成在细胞中遇到许多障碍。众所周知,翻译控制在起始步骤受到调节。翻译延伸过程是否可以反馈调节起始效率尚不清楚。密码子使用偏差是所有基因组的普遍特征,在确定基因表达水平方面起着重要作用。在这里,我们发现蛋白质丰度和 CDS 长度之间存在保守但依赖于密码子使用的全基因组负相关。密码子使用对蛋白质表达和 mRNA 核糖体通量的影响受 CDS 长度的影响;最佳密码子使用优先促进大蛋白质的产生。具有长 CDS 和非最佳密码子使用的 mRNA 的翻译优先诱导起始因子 eIF2α 的磷酸化,从而抑制翻译起始效率。删除脉孢菌中的 eIF2α 激酶 CPC-3(GCN2 同源物)优先上调由非最佳密码子编码的大蛋白。令人惊讶的是,CPC-3 还以密码子使用和 CDS 长度依赖性方式抑制翻译延伸率,导致长 CDS mRNAs 的延伸率变慢。总之,这些结果揭示了翻译延伸的密码子使用和 CDS 长度依赖性反馈机制来调节翻译起始和延伸动力学。删除脉孢菌中的 eIF2α 激酶 CPC-3(GCN2 同源物)优先上调由非最佳密码子编码的大蛋白。令人惊讶的是,CPC-3 还以密码子使用和 CDS 长度依赖性方式抑制翻译延伸率,导致长 CDS mRNAs 的延伸率变慢。总之,这些结果揭示了翻译延伸的密码子使用和 CDS 长度依赖性反馈机制来调节翻译起始和延伸动力学。删除脉孢菌中的 eIF2α 激酶 CPC-3(GCN2 同源物)优先上调由非最佳密码子编码的大蛋白。令人惊讶的是,CPC-3 还以密码子使用和 CDS 长度依赖性方式抑制翻译延伸率,导致长 CDS mRNAs 的延伸率变慢。总之,这些结果揭示了翻译延伸的密码子使用和 CDS 长度依赖性反馈机制来调节翻译起始和延伸动力学。
更新日期:2021-08-17
down
wechat
bug