The Key Parameters that Govern Translation Efficiency
The Key Parameters that Govern Translation Efficiency
复制标题
DOI：
10.1016/j.cels.2019.12.003
复制
发表时间：
2020-02-26
期刊：
影响因子：
9.3
通讯作者：
Song, Yun S.
中科院分区：
文献类型：
--
作者：
Erdmann-Pham, Dan D.;Khanh Dao Duc;Song, Yun S.
mRNA翻译成蛋白质是一个基本而复杂的生物过程，有多种因素可能影响其效率。在这里，我们研究了一个随机模型描述的交通流量的核糖体沿着的mRNA和确定的关键参数，管理的整体蛋白质合成率，起始速率变化的敏感性，和核糖体的使用效率。通过分析模型的连续极限，我们得到了稳态电流和核糖体密度的封闭形式的表达式，这与Monte Carlo模拟吻合得很好。此外，我们完全描述了系统中的相变，并通过应用我们的理论结果，我们制定了设计原则，详细说明了如何调整我们确定的关键参数，以优化翻译效率。利用S. cerevisiae，我们表明它的翻译系统是符合这些原则。我们的理论结果对进化生物学和合成生物学都有意义。
Translation of mRNA into protein is a fundamental yet complex biological process with multiple factors that can potentially affect its efficiency. Here, we study a stochastic model describing the traffic flow of ribosomes along the mRNA and identify the key parameters that govern the overall rate of protein synthesis, sensitivity to initiation rate changes, and efficiency of ribosome usage. By analyzing a continuum limit of the model, we obtain closed-form expressions for stationary currents and ribosomal densities, which agree well with Monte Carlo simulations. Furthermore, we completely characterize the phase transitions in the system, and by applying our theoretical results, we formulate design principles that detail how to tune the key parameters we identified to optimize translation efficiency. Using ribosome profiling data from S. cerevisiae, we show that its translation system is generally consistent with these principles. Our theoretical results have implications for evolutionary biology, as well as for synthetic biology.D