The dynamics of supply and demand in mRNA translation.
The dynamics of supply and demand in mRNA translation.
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mRNA翻译中的供求动力。
DOI：
10.1371/journal.pcbi.1002203
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发表时间：
2011-10
影响因子：
4.3
通讯作者：
Thiel M
中科院分区：
文献类型：
--
作者：
Brackley CA;Romano MC;Thiel M
我们研究了真核生物中mRNA翻译的延伸阶段，发现与以前模型的假设相反，对tRNA资源的供应和需求对决定延伸速率都是重要的。我们发现，提高翻译的起始率会导致某些AA-tRNA物种的耗尽，这反过来又会导致密码子缓慢和排队。在对依赖于同一tRNA资源库的多种信使核糖核酸的模拟中，观察到了特别显著的“竞争”效应。这些模拟是基于最近的伸长模型，我们使用该模型来研究酿酒酵母基因组中mRNA序列的翻译。这个模型包括了氨基酸tRNA复合体的使用和充电的动力学，我们通过蒙特卡罗模拟表明，这对系统的蛋白质生产行为有很大的影响。在本文中，我们证明了在mRNA翻译的延伸阶段，蛋白质的产生速度是可以控制的。翻译启动的调控一直是许多研究的重点，但启动速度的变化对整体翻译速度的影响，以及密码子的慢速和快速使用在mRNA序列中的作用仍不完全清楚。我们考虑了一个伸长模型，在该模型中，tRNA的使用和重新充电的动力学被考虑到真实的mRNA序列。我们发现，tRNA的需求和供应之间的平衡对于决定翻译速度是至关重要的。当考虑多个信使核糖核酸的同时翻译时，观察到特别有趣的“竞争”效应。我们确实证明，通过选择慢或快密码子，原则上可以控制tRNA资源的供需变化如何改变不同mRNA产生蛋白质的速度。
We study the elongation stage of mRNA translation in eukaryotes and find that, in contrast to the assumptions of previous models, both the supply and the demand for tRNA resources are important for determining elongation rates. We find that increasing the initiation rate of translation can lead to the depletion of some species of aa-tRNA, which in turn can lead to slow codons and queueing. Particularly striking “competition” effects are observed in simulations of multiple species of mRNA which are reliant on the same pool of tRNA resources. These simulations are based on a recent model of elongation which we use to study the translation of mRNA sequences from the Saccharomyces cerevisiae genome. This model includes the dynamics of the use and recharging of amino acid tRNA complexes, and we show via Monte Carlo simulation that this has a dramatic effect on the protein production behaviour of the system. In this paper we show that the rate at which proteins are produced can be controlled at the elongation stage of mRNA translation. Regulation of translation initiation has been a focus of much study, but the subsequent effect of changes in the initiation rate on the overall translation rate, and the role of slow and fast codon usage in mRNA sequences is still not fully understood. We consider a model of elongation in which the dynamics of tRNA use and recharging are considered for real mRNA sequences. We find that the balance between the demand for, and supply of tRNAs is crucial in determining translation rates. Particularly interesting “competition” effects are observed when the simultaneous translation of multiple mRNA is considered. We show indeed that, via the choice of slow or fast codons, it is in principle possible to control how variation of the supply and demand for tRNA resources changes the rate of protein production from different mRNAs.
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