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.

中文翻译：

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破译mRNA序列决定蛋白的生产率

翻译的生物物理模型中的最大挑战之一就是要确定编码序列特征，这些特征会影响翻译的速率，从而影响细胞中蛋白质的整体产量。我们提出一种解析方法来解决基于不均匀的完全不对称简单排除过程的翻译模型，这使我们能够揭示确定蛋白质生产速度的核苷酸序列的简单设计原理。与酿酒酵母的全基因组数值模拟相比，我们的解决方案具有极好的一致性。转录序列，并预测前10个密码子（即mRNA上的核糖体足迹长度）以及起始速率的值，是生理条件下蛋白质生产速率的主要决定因素。最后，我们根据密码子选择对调节翻译速率和核糖体密度的进化作用来解释获得的分析结果。