9 Mechanism of Translation Initiation in the Yeast Saccharomyces cerevisiae
9 Mechanism of Translation Initiation in the Yeast Saccharomyces cerevisiae
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9 酿酒酵母翻译起始机制
DOI：
10.1101/087969767.48.225
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发表时间：
2007
期刊：
影响因子：
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通讯作者：
K. Asano
中科院分区：
文献类型：
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作者：
A. Hinnebusch;T. Dever;K. Asano
我们对翻译起始途径的理解主要基于对纯化的哺乳动物因子的生化分析，如第 4 章所述。酿酒酵母的遗传和生化分析有助于阐明该途径中的分子机制，而酵母的遗传研究为建立使用无细胞系统得出的结论的生理相关性提供了最佳机会，从而为本次综述提供了动力。根据目前的模型（图1），该途径开始于在eIF1、eIF1A和eIF3促进的反应中与包含eIF2、GTP和Met-tRNA i Met的三元复合物（TC）的游离40S亚基结合。由此形成的 43S 前起始复合物 (PIC) 在 eIF4F、-4A、-4B 和聚腺苷酸结合蛋白 (PABP) 的帮助下与 mRNA 结合，并扫描 mRNA 的起始密码子。 Met-tRNA i Met 与 AUG 的碱基配对刺激与 eIF2 结合的 GTP 水解，依赖于 GTP 酶激活蛋白 (GAP) eIF5 和 40S 亚基，释放 eIF2-GDP 等因子，eIF5B-GTP 刺激 60S 亚基连接。 eIF2-GDP 必须通过鸟嘌呤核苷酸交换因子 (GEF) eIF2B 循环至 eIF2-GTP，以进行新一轮的启动，并且在应激条件下，eIF2 α 亚基 Ser-51 上的磷酸化会抑制该反应。我们对 Met-tRNA i Met 募集的机制和调节的了解的许多进展来自于对 eIF2α 激酶 GCN2（通用控制 n 去阻遏物 2）对酵母 GCN4 mRNA 翻译控制的遗传分析。氨基酸饥饿激活 GCN2 会产生……
Our understanding of the translation initiation pathway is based largely on biochemical analysis of purified mammalian factors, as described in Chapter 4. Genetic and biochemical analysis of the yeast Saccharomyces cerevisiae is helping to elucidate molecular mechanisms in the pathway, and genetic studies in yeast provide the best opportunity to establish the physiological relevance of conclusions reached using cell-free systems, thus providing the impetus for this review. According to the current model (Fig. 1), the pathway begins with binding to the free 40S subunit of a ternary complex (TC) comprising eIF2, GTP, and Met-tRNA i Met , in a reaction promoted by eIF1, eIF1A, and eIF3. The 43S preinitiation complex (PIC) thus formed binds to the mRNA, with the assistance of eIF4F, -4A, -4B, and poly(A)-binding protein (PABP), and scans the mRNA for the start codon. Base-pairing of Met-tRNA i Met with AUG stimulates hydrolysis of the GTP bound to eIF2, dependent on the GTPase-activating protein (GAP) eIF5 and 40S subunit, the eIF2-GDP and other factors are released, and eIF5B-GTP stimulates 60S subunit joining. The eIF2-GDP must be recycled to eIF2-GTP by the guanine nucleotide exchange factor (GEF) eIF2B for a new round of initiation, and this reaction is inhibited under stress conditions by phosphorylation of the α subunit of eIF2 on Ser-51. Many advances in our knowledge of the mechanism and regulation of Met-tRNA i Met recruitment have come from genetic analysis of translational control of yeast GCN4 mRNA by the eIF2α kinase GCN2 ( g eneral c ontrol n on-derepressible 2). Activation of GCN2 by amino acid starvation produces...