SUPA, School of Physics and Astronomy, University of Edinburgh, Peter Guthrie Tait Road, Edinburgh EH9 3FD, United Kingdom.
L2C, Université de Montpellier, CNRS, Montpellier, France and DIMNP, Université de Montpellier, CNRS, Montpellier, France.
Phys Rev Lett. 2018 Mar 23;120(12):128101. doi: 10.1103/PhysRevLett.120.128101.
One of the greatest challenges in biophysical models of translation is to identify coding sequence features that affect the rate of translation and therefore the overall protein production in the cell. We propose an analytic method to solve a translation model based on the inhomogeneous totally asymmetric simple exclusion process, which allows us to unveil simple design principles of nucleotide sequences determining protein production rates. Our solution shows an excellent agreement when compared to numerical genome-wide simulations of S. cerevisiae transcript sequences and predicts that the first 10 codons, which is the ribosome footprint length on the mRNA, together with the value of the initiation rate, are the main determinants of protein production rate under physiological conditions. Finally, we interpret the obtained analytic results based on the evolutionary role of the codons' choice for regulating translation rates and ribosome densities.
在翻译的生物物理模型中，最大的挑战之一是确定影响翻译速度的编码序列特征，从而影响细胞内的整体蛋白质产量。我们提出了一种分析方法来解决基于非均匀完全非对称简单排斥过程的翻译模型，这使我们能够揭示决定蛋白质产生速率的核苷酸序列的简单设计原则。与酿酒酵母转录序列的全基因组数值模拟相比，我们的解决方案显示出极好的一致性，并预测在生理条件下，第一个 10 个密码子（核糖体在 mRNA 上的足迹长度）以及起始速率值是决定蛋白质产生速率的主要决定因素。最后，我们根据密码子选择在调节翻译速率和核糖体密度方面的进化作用来解释所得到的分析结果。
