An in vivo control map for the eukaryotic mRNA translation machinery.

An in vivo control map for the eukaryotic mRNA translation machinery.
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DOI:
10.1038/msb.2012.73
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发表时间:
2013
影响因子:
9.9
通讯作者:
--
中科院分区:
生物学1区
文献类型:
--
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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的数字模型。在其他非直观的结果中,翻译表现出高度的功能模块化,并由非化学计量组合的蛋白质组成,这些蛋白质在共享的最大翻译速率上表现出功能趋同。在指数生长的细胞中,多肽延长(eEF1a、eEF2和eEF3)发挥了最强的控制作用。另外两个强控制点是40S核糖体亚基(eIF4F和eIF2)的mRNA和tRNAi的募集和终止(eRF1;Dbp5)。相反,在比平均水平更长的5‘非翻译区(eIF1、eIF1A、Ded1、eIF2B、eIF3和eIF5)上,发现促进mRNA扫描效率的因子超过了最大限度控制所需的水平。这有望使细胞最大限度地减少扫描转换时间,特别是对于较长的5‘UTRs。分析揭示了这些和其他集体适应的控制共享的因素,以及反映功能模块化和系统健壮性的功能。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。
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 tRNAi 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.
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