microRNA作用于蛋白质翻译过程的动力学模型
Dynamical modeling of microRNA action on the protein translation process
摘要：
蛋白质翻译是一个多步骤的过程，可以表示为一系列生化反应（起始、核糖体组装、延伸等），其速率可以通过多种机制由小的非编码microRNA调节。目前还不清楚什么样的microRNA作用机制是最主要的：此外，许多实验报告提供了关于实验中实际观察到的具体机制的相互矛盾的信息。Parker和Nissan（Parker和Nissan，RNA，2008）证明，使用蛋白质合成速率的稳态数据无法区分替代生物学假设。在他们的分析中，他们使用了两种简单的蛋白质翻译动力学模型。相反，我们表明，动态数据允许区分一些microRNA作用的机制。为了比较，我们使用与（Parker和Nissan，RNA，2008）中相同的模型来证明这一点，但是所开发的方法（生化网络的渐近性）可以用于其他模型。作为我们分析的结果之一，我们提出了一个假设，即只有当microRNA作用影响蛋白质翻译机制的主导系统（复杂网络的限制步骤概念的推广）时，它的作用才是可测量和可观察的。在不同的实验条件下，主导体系可能会有所不同，这可以部分解释一些实验数据存在的争议。
英文摘要：
Protein translation is a multistep process which can be represented as a cascade of biochemical reactions (initiation, ribosome assembly, elongation, etc.), the rate of which can be regulated by small non-coding microRNAs through multiple mechanisms. It remains unclear what mechanisms of microRNA action are most dominant: moreover, many experimental reports deliver controversal messages on what is the concrete mechanism actually observed in the experiment. Parker and Nissan (Parker and Nissan, RNA, 2008) demonstrated that it is impossible to distinguish alternative biological hypotheses using the steady state data on the rate of protein synthesis. For their analysis they used two simple kinetic models of protein translation. In contrary, we show that dynamical data allow to discriminate some of the mechanisms of microRNA action. We demonstrate this using the same models as in (Parker and Nissan, RNA, 2008) for the sake of comparison but the methods developed (asymptotology of biochemical networks) can be used for other models. As one of the results of our analysis, we formulate a hypothesis that the effect of microRNA action is measurable and observable only if it affects the dominant system (generalization of the limiting step notion for complex networks) of the protein translation machinery. The dominant system can vary in different experimental conditions that can partially explain the existing controversy of some of the experimental data.
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