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An in vivo control map for the eukaryotic mRNA translation machinery.
Molecular Systems Biology ( IF 9.9 ) Pub Date : 2013-01-01 , DOI: 10.1038/msb.2012.73
Helena Firczuk 1 , Shichina Kannambath , Jürgen Pahle , Amy Claydon , Robert Beynon , John Duncan , Hans Westerhoff , Pedro Mendes , John Eg McCarthy
Affiliation  

Rate control analysis defines the in vivo control map governing yeast protein synthesis and generates an extensively parameterized digital model of the translation pathway. Among other non-intuitive outcomes, translation demonstrates a high degree of functional modularity and comprises a non-stoichiometric combination of proteins manifesting functional convergence on a shared maximal translation rate. In exponentially growing cells, polypeptide elongation (eEF1A, eEF2, and eEF3) exerts the strongest control. The two other strong control points are recruitment of mRNA and tRNA(i) to the 40S ribosomal subunit (eIF4F and eIF2) and termination (eRF1; Dbp5). In contrast, factors that are found to promote mRNA scanning efficiency on a longer than-average 5'untranslated region (eIF1, eIF1A, Ded1, eIF2B, eIF3, and eIF5) exceed the levels required for maximal control. This is expected to allow the cell to minimize scanning transition times, particularly for longer 5'UTRs. The analysis reveals these and other collective adaptations of control shared across the factors, as well as features that reflect functional modularity and system robustness. Remarkably, gene duplication is implicated in the fine control of cellular protein synthesis.

中文翻译:

真核 mRNA 翻译机制的体内控制图。

速率控制分析定义了控制酵母蛋白质合成的体内控制图,并生成了翻译途径的广泛参数化数字模型。在其他非直观结果中,翻译表现出高度的功能模块性,并包括蛋白质的非化学计量组合,在共享的最大翻译速率上表现出功能收敛。在指数生长的细胞中,多肽伸长(eEF1A、eEF2 和 eEF3)发挥最强的控制作用。另外两个强有力的控制点是将 mRNA 和 tRNA(i) 募集到 40S 核糖体亚基(eIF4F 和 eIF2)和终止(eRF1;Dbp5)。相比之下,发现在比平均长度更长的 5' 非翻译区(eIF1、eIF1A、Ded1、eIF2B、eIF3、和 eIF5) 超过最大控制所需的水平。预计这将使单元最小化扫描转换时间,特别是对于较长的 5'UTR。分析揭示了这些和其他跨因素共享的控制集体适应性,以及反映功能模块化和系统稳健性的特征。值得注意的是,基因复制与细胞蛋白质合成的精细控制有关。
更新日期:2019-11-01
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