Department of Electrical Engineering-Systems, Faculty of Engineering, Tel Aviv University, 69978, Tel Aviv, Israel.
Department of Biomedical Engineering, Faculty of Engineering, Tel Aviv University, 69978, Tel Aviv, Israel.
Sci Rep. 2021 Mar 5;11(1):5300. doi: 10.1038/s41598-021-84738-0.
The rate of mRNA translation depends on the initiation, elongation, and termination rates of ribosomes along the mRNA. These rates depend on many "local" factors like the abundance of free ribosomes and tRNA molecules in the vicinity of the mRNA molecule. All these factors are stochastic and their experimental measurements are also noisy. An important question is how protein production in the cell is affected by this considerable variability. We develop a new theoretical framework for addressing this question by modeling the rates as identically and independently distributed random variables and using tools from random matrix theory to analyze the steady-state production rate. The analysis reveals a principle of universality: the average protein production rate depends only on the of the set of possible values that the random variable may attain. This explains how total protein production can be stabilized despite the overwhelming stochasticticity underlying cellular processes.
mRNA 翻译的速度取决于核糖体在 mRNA 上的起始、延伸和终止速度。这些速度取决于许多“局部”因素,如游离核糖体和 tRNA 分子在 mRNA 分子附近的丰度。所有这些因素都是随机的,它们的实验测量也是有噪声的。一个重要的问题是细胞中的蛋白质生产是如何受到这种相当大的可变性的影响的。我们通过将速率建模为相同且独立分布的随机变量,并使用随机矩阵理论的工具来分析稳态生产速率,从而为解决这个问题开发了一个新的理论框架。分析揭示了一个普遍性原则:平均蛋白质生产速率仅取决于随机变量可能达到的可能值集。这解释了尽管细胞过程的基础是压倒性的随机性,总蛋白生产如何能够稳定下来。