4真核生物翻译起始机制

T. Pestova, J. Lorsch, C. Hellen
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引用次数: 43

摘要

真核生物的标准翻译起始是导致80S核糖体在mRNA上组装的过程,其中起始密码子与核糖体肽基(P)位点上氨基酰化启动物甲硫基转移RNA (Met- trna i Met)的CAU反密码子碱基配对。该过程需要分离小(40S)和大(60S)核糖体亚基,涉及至少12个真核起始因子(eIFs)以及ATP和GTP的结合和水解。由此产生的80S起始复合物能够进入翻译的延伸期。本章描述了5 '端依赖起始的典型机制,侧重于高等真核生物的起始过程。这一过程与植物和酵母中的过程在细节上有所不同,在植物和酵母中,亚基结构和一些因素的组成有很大的不同。关于酵母起始和植物起始的更详细的综述,分别见第9章和第26章。有关内部核糖体进入机制的回顾,请参见第5章和第6章。真核细胞质mrna的翻译效率受起始速率的限制(参见Palmiter 1972),而起始速率又由mrna的结构特征决定,这些结构特征会影响核糖体的招募、对起始密码子的扫描以及起始密码子的识别。真核mrna与介导核输出、亚细胞定位、稳定性和翻译抑制的蛋白质动态关联,因此作为信使核糖核蛋白(mRNPs)而不是作为自由多核苷酸存在于细胞中。mRNP蛋白对起始的影响不在本文的讨论范围之内。几乎……
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4 The Mechanism of Translation Initiation in Eukaryotes
Standard translation initiation in eukaryotes is the process that leads to assembly of an 80S ribosome on an mRNA in which the initiation codon is base-paired to the CAU anticodon of aminoacylated initiator methionyl-transfer RNA (Met-tRNA i Met ) in the ribosomal peptidyl (P) site. The process requires separated small (40S) and large (60S) ribosomal subunits and involves at least 12 eukaryotic initiation factors (eIFs) and the binding and hydrolysis of ATP and GTP. The resulting 80S initiation complex is competent to enter the elongation phase of translation. This chapter describes the canonical mechanism of 5′-end-dependent initiation, with a bias toward the initiation process in higher eukaryotes. This process differs in detail from that in plants and yeast, in which the subunit structure and composition of some factors differ substantially. For a more detailed review of initiation in yeast and in plants, see Chapters 9 and 26, respectively. For a review of mechanisms dependent on internal ribosome entry, see Chapters 5 and 6. STRUCTURE OF EUKARYOTIC CYTOPLASMIC mRNAs The translational efficiency of eukaryotic mRNAs is limited by the rate of initiation (see, e.g., Palmiter 1972), which is in turn determined by structural features of mRNAs that influence ribosomal recruitment, scanning to the initiation codon, and initiation codon recognition. Eukaryotic mRNAs associate dynamically with proteins that mediate nuclear export, subcellular localization, stability, and translational repression, and therefore exist in cells as messenger ribonucleoproteins (mRNPs) rather than as free polynucleotides. The influence of mRNP proteins on initiation is outside the scope of this review. Almost...
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