Department of Biomedical Engineering, Tel-Aviv University, Tel-Aviv, Israel.
Department of Biomedical Engineering and the Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, Israel.
PLoS Comput Biol. 2018 Apr 3;14(4):e1006055. doi: 10.1371/journal.pcbi.1006055. eCollection 2018 Apr.
Recent studies have demonstrated how the competition for the finite pool of available gene expression factors has important effect on fundamental gene expression aspects. In this study, based on a whole-cell model simulation of translation in S. cerevisiae, we evaluate for the first time the expected effect of mRNA levels fluctuations on translation due to the finite pool of ribosomes. We show that fluctuations of a single gene or a group of genes mRNA levels induce periodic behavior in all S. cerevisiae translation factors and aspects: the ribosomal densities and the translation rates of all S. cerevisiae mRNAs oscillate. We numerically measure the oscillation amplitudes demonstrating that fluctuations of endogenous and heterologous genes can cause a significant fluctuation of up to 50% in the steady-state translation rates of the rest of the genes. Furthermore, we demonstrate by synonymous mutations that oscillating the levels of mRNAs that experience high ribosomal occupancy (e.g. ribosomal "traffic jam") induces the largest impact on the translation of the S. cerevisiae genome. The results reported here should provide novel insights and principles related to the design of synthetic gene expression circuits and related to the evolutionary constraints shaping gene expression of endogenous genes.
最近的研究表明，有限的基因表达因子竞争如何对基本的基因表达方面产生重要影响。在这项研究中，我们基于酿酒酵母翻译的全细胞模型模拟，首次评估了由于核糖体的有限池，mRNA 水平波动对翻译的预期影响。我们表明，单个基因或一组基因的 mRNA 水平波动会引起所有酿酒酵母翻译因子和方面的周期性行为：核糖体密度和所有酿酒酵母 mRNA 的翻译速率都在波动。我们通过数值测量了振荡幅度，证明内源性和异源基因的波动可以导致其余基因的稳态翻译速率显著波动高达 50%。此外，我们通过同义突变证明，波动经历高核糖体占有率（例如核糖体“交通堵塞”）的 mRNA 水平会对酿酒酵母基因组的翻译产生最大影响。这里报告的结果应该为设计合成基因表达电路以及与塑造内源性基因表达的进化限制相关的设计提供新的见解和原则。
