细胞内核糖体竞争模型
A Model for Competition for Ribosomes in the Cell
摘要：
大规模的同时mRNA翻译和由此产生的对可用核糖体的竞争对细胞的功能和进化具有重要意义。更好地理解这些同步过程之间的复杂相关性，而不是专注于单个孤立转录本的翻译，应该有助于更好地理解mRNA翻译调控以及延伸率影响生物体适应性的方式。当处理高表达基因时，同步翻译模型特别重要，因为这些基因消耗更多的资源。此外，这样的模型可以导致更准确的预测，需要在合成生物学中的翻译模块的互连。我们开发和分析了一个通用的大规模同时mRNA翻译和竞争核糖体的模型。这是基于结合几个核糖体流动模型（RFM）通过一个池的自由核糖体互连。我们证明，该复合系统总是收敛到一个稳定的状态，它总是夹带或锁相周期性随时间变化的过渡率在任何的mRNA分子。我们使用这个模型来探索稳态下各种mRNA分子和核糖体之间的相互作用。我们发现，增加mRNA分子的长度会降低所有mRNA的产生速率。增加特定mRNA分子中的任何密码子翻译速率都会产生局部效应：该mRNA的翻译速率增加，以及全局效应：其他mRNA分子中的翻译速率全部增加或全部减少。这些结果表明，内源和异源mRNA的密码子解码速率对蛋白质产生的影响比以前认为的更复杂。
英文摘要：
Large-scale simultaneous mRNA translation and the resulting competition for the available ribosomes has important implications to the cell's functioning and evolution. Developing a better understanding of the intricate correlations between these simultaneous processes, rather than focusing on the translation of a single isolated transcript, should help in gaining a better understanding of mRNA translation regulation and the way elongation rates affect organismal fitness. A model of simultaneous translation is specifically important when dealing with highly expressed genes, as these consume more resources. In addition, such a model can lead to more accurate predictions that are needed in the interconnection of translational modules in synthetic biology. We develop and analyze a general model for large-scale simultaneous mRNA translation and competition for ribosomes. This is based on combining several ribosome flow models (RFMs) interconnected via a pool of free ribosomes. We prove that the compound system always converges to a steady-state and that it always entrains or phase locks to periodically time-varying transition rates in any of the mRNA molecules. We use this model to explore the interactions between the various mRNA molecules and ribosomes at steady-state. We show that increasing the length of an mRNA molecule decreases the production rate of all the mRNAs. Increasing any of the codon translation rates in a specific mRNA molecule yields a local effect: an increase in the translation rate of this mRNA, and also a global effect: the translation rates in the other mRNA molecules all increase or all decrease. These results suggest that the effect of codon decoding rates of endogenous and heterologous mRNAs on protein production is more complicated than previously thought.
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