Minimum-noise production of translation factor eIF4G maps to a mechanistically determined optimal rate control window for protein synthesis.
Minimum-noise production of translation factor eIF4G maps to a mechanistically determined optimal rate control window for protein synthesis.
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DOI：
10.1093/nar/gkw1194
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发表时间：
2017-01-25
影响因子：
14.9
通讯作者：
McCarthy JE
中科院分区：
文献类型：
--
作者：
Meng X;Firczuk H;Pietroni P;Westbrook R;Dacheux E;Mendes P;McCarthy JE
基因表达噪声影响生物进化和适应性。决定随机性和翻译机器组件的功能作用之间的关系的机制是至关重要的生存能力。eIF4G是一种重要的翻译因子，对蛋白质合成发挥强有力的控制作用。我们观察到一个不对称的，近似钟形，eIF4G的平均细胞内丰度和细胞群体的增长率和全球mRNA的翻译之间的关系，峰值发生在正常的生理丰度。这种关系符合计算模型，其中eIF4G是多组分复合物组装途径的核心。该模型还正确地预测了其他帽复合物因子eIF4E和eIF4A丰度的超生理增加的翻译平台样反应。eIF4G丰度的工程变化放大了噪音，表明最小的随机性与该因子的生理丰度一致。当eIF4E过量产生时，噪声不会增加。质粒介导的eIF4G合成增加了整体基因表达的随机性，降低了活力，因为该因子的内在噪音影响总的细胞基因噪音。自然进化的eIF4G基因表达噪音最小图内的最佳活性区由eIF4G的机械作用。因此，速率控制和噪声是相互依赖的，并且共同进化以共享最佳生理丰度点。
Gene expression noise influences organism evolution and fitness. The mechanisms determining the relationship between stochasticity and the functional role of translation machinery components are critical to viability. eIF4G is an essential translation factor that exerts strong control over protein synthesis. We observe an asymmetric, approximately bell-shaped, relationship between the average intracellular abundance of eIF4G and rates of cell population growth and global mRNA translation, with peak rates occurring at normal physiological abundance. This relationship fits a computational model in which eIF4G is at the core of a multi-component–complex assembly pathway. This model also correctly predicts a plateau-like response of translation to super-physiological increases in abundance of the other cap-complex factors, eIF4E and eIF4A. Engineered changes in eIF4G abundance amplify noise, demonstrating that minimum stochasticity coincides with physiological abundance of this factor. Noise is not increased when eIF4E is overproduced. Plasmid-mediated synthesis of eIF4G imposes increased global gene expression stochasticity and reduced viability because the intrinsic noise for this factor influences total cellular gene noise. The naturally evolved eIF4G gene expression noise minimum maps within the optimal activity zone dictated by eIF4G's mechanistic role. Rate control and noise are therefore interdependent and have co-evolved to share an optimal physiological abundance point.