A quantitative model for mRNA translation in Saccharomyces cerevisiae
A quantitative model for mRNA translation in Saccharomyces cerevisiae
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DOI：
10.1002/yea.1770
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发表时间：
2010-10-01
期刊：
影响因子：
2.6
通讯作者：
Brown, Alistair J. P.
中科院分区：
文献类型：
--
作者：
You, Tao;Coghill, George M.;Brown, Alistair J. P.
信使核糖核酸(Messenger RNA，mRNA)的翻译是真核基因表达过程中的一个重要步骤，参与了这一过程的调控。我们描述了一个基于常微分方程式的确定性模型，该模型描述了酿酒酵母中的mRNA翻译。该模型利用已发表的数据进行了参数化，旨在研究翻译启动因子对氨基酸可用性的反应动力学行为。该模型预测，在氨基酸饥饿的条件下，eIF1-eIF3-eIF5复合体的丰度增加，这表明除了eIF2的已知机制外，这些因素在调节翻译启动方面可能还有辅助作用。我们对mRNA翻译模型的稳健性的分析表明，随机产生的群体中的单个细胞通过GCN2信号对外部扰动(如氨基酸可获得性的变化)敏感。然而，该模型预测，单个细胞对内部扰动(如翻译起始因子和动力学参数丰度的变化)表现出稳健性。GCN2似乎增强了系统内的这种稳健性。这些发现表明，这个生物网络的健壮性和性能之间存在权衡。该模型还预测，由于随机的内部扰动，单个细胞在其绝对翻译率方面表现出相当大的异质性。因此，平均细胞群体的运动行为可能会掩盖单个细胞的动态稳健性。这突出了单小区测量对于评估网络属性的重要性。版权所有(C)2010 John Wiley&Sons，Ltd.
Messenger RNA (mRNA) translation is an essential step in eukaryotic gene expression that contributes to the regulation of this process. We describe a deterministic model based on ordinary differential equations that describe mRNA translation in Saccharomyces cerevisiae. This model, which was parameterized using published data, was developed to examine the kinetic behaviour of translation initiation factors in response to amino acid availability. The model predicts that the abundance of the eIF1-eIF3-eIF5 complex increases under amino acid starvation conditions, suggesting a possible auxiliary role for these factors in modulating translation initiation in addition to the known mechanisms involving eIF2. Our analyses of the robustness of the mRNA translation model suggest that individual cells within a randomly generated population are sensitive to external perturbations (such as changes in amino acid availability) through Gcn2 signalling. However, the model predicts that individual cells exhibit robustness against internal perturbations (such as changes in the abundance of translation initiation factors and kinetic parameters). Gcn2 appears to enhance this robustness within the system. These findings suggest a trade-off between the robustness and performance of this biological network. The model also predicts that individual cells exhibit considerable heterogeneity with respect to their absolute translation rates, due to random internal perturbations. Therefore, averaging the kinetic behaviour of cell populations probably obscures the dynamic robustness of individual cells. This highlights the importance of single-cell measurements for evaluating network properties. Copyright (C) 2010 John Wiley & Sons, Ltd.