Gorochowski Thomas E, Ignatova Zoya, Bovenberg Roel A L, Roubos Johannes A
DSM Biotechnology Center, P.O. Box 1, 2600 MA Delft, The Netherlands
Department of Biochemistry, Institute of Biochemistry and Biology, University of Potsdam, 14476 Potsdam-Golm, Germany Biochemistry and Molecular Biology, Department of Chemistry, University of Hamburg, 20146 Hamburg, Germany.
Nucleic Acids Res. 2015 Mar 31;43(6):3022-32. doi: 10.1093/nar/gkv199. Epub 2015 Mar 12.
Translation of protein from mRNA is a complex multi-step process that occurs at a non-uniform rate. Variability in ribosome speed along an mRNA enables refinement of the proteome and plays a critical role in protein biogenesis. Detailed single protein studies have found both tRNA abundance and mRNA secondary structure as key modulators of translation elongation rate, but recent genome-wide ribosome profiling experiments have not observed significant influence of either on translation efficiency. Here we provide evidence that this results from an inherent trade-off between these factors. We find codons pairing to high-abundance tRNAs are preferentially used in regions of high secondary structure content, while codons read by significantly less abundant tRNAs are located in lowly structured regions. By considering long stretches of high and low mRNA secondary structure in Saccharomyces cerevisiae and Escherichia coli and comparing them to randomized-gene models and experimental expression data, we were able to distinguish clear selective pressures and increased protein expression for specific codon choices. The trade-off between secondary structure and tRNA-concentration based codon choice allows for compensation of their independent effects on translation, helping to smooth overall translational speed and reducing the chance of potentially detrimental points of excessively slow or fast ribosome movement.
从信使核糖核酸（mRNA）翻译蛋白质是一个复杂的多步骤过程，其发生速率并不均匀。核糖体沿mRNA移动速度的变化能够优化蛋白质组，并且在蛋白质生物合成中起着关键作用。详细的单一蛋白质研究发现，转运核糖核酸（tRNA）丰度和mRNA二级结构都是翻译延伸速率的关键调节因子，但最近的全基因组核糖体分析实验并未观察到二者对翻译效率有显著影响。在此，我们提供证据表明，这是由于这些因素之间存在内在的权衡。我们发现，与高丰度tRNA配对的密码子优先用于二级结构含量高的区域，而由丰度显著较低的tRNA读取的密码子则位于二级结构较少的区域。通过考虑酿酒酵母和大肠杆菌中长片段的高二级结构和低二级结构mRNA，并将它们与随机基因模型及实验表达数据进行比较，我们能够区分出明确的选择压力以及特定密码子选择对蛋白质表达的增强作用。基于二级结构与tRNA浓度的密码子选择之间的权衡，能够补偿它们对翻译的独立影响，有助于使整体翻译速度平稳，并减少核糖体移动过慢或过快的潜在有害点出现的几率。
