In living organisms, the same enzyme catalyses the degradation of thousands of different mRNAs, but the possible influence of competing substrates has been largely ignored so far. We develop a simple mechanistic model of the coupled degradation of all cell mRNAs using the total quasi-steady-state approximation of the Michaelis–Menten framework. Numerical simulations of the model using carefully chosen parameters and analyses of rate sensitivity coefficients show how substrate competition alters mRNA decay. The model predictions reproduce and explain a number of experimental observations on mRNA decay following transcription arrest, such as delays before the onset of degradation, the occurrence of variable degradation profiles with increased non linearities and the negative correlation between mRNA half-life and concentration. The competition acts at different levels, through the initial concentration of cell mRNAs and by modifying the enzyme affinity for its targets. The consequence is a global slow down of mRNA decay due to enzyme titration and the amplification of its apparent affinity. Competition happens to stabilize weakly affine mRNAs and to destabilize the most affine ones. We believe that this mechanistic model is an interesting alternative to the exponential models commonly used for the determination of mRNA half-lives. It allows analysing regulatory mechanisms of mRNA degradation and its predictions are directly comparable to experimental data.

在活生物体中，相同的酶催化数千种不同mRNA的降解，但是迄今为止，竞争底物的可能影响已被很大程度上忽略。我们使用Michaelis-Menten框架的总准稳态近似，开发了一个简单的机械模型，用于耦合降解所有细胞mRNA。使用精心选择的参数对模型进行的数值模拟以及对速率敏感性系数的分析表明，底物竞争如何改变mRNA的衰减。该模型预测重现并解释了许多有关转录停滞后mRNA降解的实验观察结果，例如降解开始之前的延迟，非线性增加的可变降解图的出现以及mRNA半衰期与浓度之间的负相关。竞争通过细胞mRNA的初始浓度和修饰酶对其靶标的亲和力而发挥不同的作用。结果是由于酶滴定和其表观亲和力的扩增而导致的mRNA衰减的整体减慢。竞争恰好使弱仿射mRNA稳定并使最仿射mRNA不稳定。我们认为，该机制模型是通常用于确定mRNA半衰期的指数模型的有趣替代方法。它可以分析mRNA降解的调控机制，其预测与实验数据可直接比较。结果是由于酶滴定和其表观亲和力的扩增而导致的mRNA衰减的整体减慢。竞争恰好使弱仿射mRNA稳定并使最仿射mRNA不稳定。我们认为，该机制模型是通常用于确定mRNA半衰期的指数模型的有趣替代方法。它可以分析mRNA降解的调控机制，其预测与实验数据可直接比较。结果是由于酶滴定和其表观亲和力的扩增而导致的mRNA衰减的整体减慢。竞争恰好使弱仿射mRNA稳定并使最仿射mRNA不稳定。我们认为，该机制模型是通常用于确定mRNA半衰期的指数模型的有趣替代方法。它可以分析mRNA降解的调控机制，其预测与实验数据可直接比较。