真核生物翻译起始的机制：新的见解和挑战。
The mechanism of eukaryotic translation initiation: new insights and challenges.
机构信息
Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
出版信息
Cold Spring Harb Perspect Biol. 2012 Oct 1;4(10):a011544. doi: 10.1101/cshperspect.a011544.
Abstract
Translation initiation in eukaryotes is a highly regulated and complex stage of gene expression. It requires the action of at least 12 initiation factors, many of which are known to be the targets of regulatory pathways. Here we review our current understanding of the molecular mechanics of eukaryotic translation initiation, focusing on recent breakthroughs from in vitro and in vivo studies. We also identify important unanswered questions that will require new ideas and techniques to solve.
摘要
真核生物的翻译起始是一个高度调控和复杂的基因表达阶段。它需要至少 12 种起始因子的作用，其中许多因子是已知的调节途径的靶标。在这里，我们回顾了我们对真核翻译起始的分子机制的现有认识，重点介绍了来自体外和体内研究的最新突破。我们还确定了一些重要的未解决问题，这些问题需要新的思路和技术来解决。
相似文献
1
The mechanism of eukaryotic translation initiation: new insights and challenges.真核生物翻译起始的机制：新的见解和挑战。
Cold Spring Harb Perspect Biol. 2012 Oct 1;4(10):a011544. doi: 10.1101/cshperspect.a011544.
2
Mechanism of ribosomal subunit joining during eukaryotic translation initiation.真核生物翻译起始过程中核糖体亚基结合的机制。
Biochem Soc Trans. 2008 Aug;36(Pt 4):653-7. doi: 10.1042/BST0360653.
3
Structural insights into eukaryotic ribosomes and the initiation of translation.真核核糖体与翻译起始的结构研究进展
Curr Opin Struct Biol. 2012 Dec;22(6):768-77. doi: 10.1016/j.sbi.2012.07.010. Epub 2012 Aug 10.
4
Four translation initiation pathways employed by the leaderless mRNA in eukaryotes.真核生物中无帽子 mRNA 采用的四种翻译起始途径。
Sci Rep. 2016 Nov 28;6:37905. doi: 10.1038/srep37905.
5
The structure and function of the eukaryotic ribosome.真核核糖体的结构与功能。
Cold Spring Harb Perspect Biol. 2012 May 1;4(5):a011536. doi: 10.1101/cshperspect.a011536.
6
Elucidating mechanistic principles underpinning eukaryotic translation initiation using quantitative fluorescence methods.利用定量荧光方法阐明真核翻译起始的机制原理。
Biochem Soc Trans. 2010 Dec;38(6):1587-92. doi: 10.1042/BST0381587.
7
Structural Insights into the Mechanism of Scanning and Start Codon Recognition in Eukaryotic Translation Initiation.结构洞察真核翻译起始中扫描和起始密码子识别的机制。
Trends Biochem Sci. 2017 Aug;42(8):589-611. doi: 10.1016/j.tibs.2017.03.004. Epub 2017 Apr 22.
8
'Ribozoomin'--translation initiation from the perspective of the ribosome-bound eukaryotic initiation factors (eIFs).“Ribozoomin'——从核糖体结合的真核起始因子 (eIFs) 的角度看翻译起始。”
Curr Protein Pept Sci. 2012 Jun;13(4):305-30. doi: 10.2174/138920312801619385.
9
Insights into the mechanisms of eukaryotic translation gained with ribosome profiling.通过核糖体分析对真核生物翻译机制的深入了解。
Nucleic Acids Res. 2017 Jan 25;45(2):513-526. doi: 10.1093/nar/gkw1190. Epub 2016 Dec 6.
10
Universal translation initiation factor IF2/eIF5B.通用翻译起始因子IF2/eIF5B
Cold Spring Harb Symp Quant Biol. 2001;66:417-24. doi: 10.1101/sqb.2001.66.417.
引用本文的文献
1
Extra-Ribosomal Roles for Ribosomal Proteins and Their Relevance to Tumour Suppression, Carcinogenesis and Cancer Progression.核糖体蛋白的核糖体外功能及其与肿瘤抑制、致癌作用和癌症进展的相关性。
Cancers (Basel). 2025 Aug 29;17(17):2825. doi: 10.3390/cancers17172825.
2
Translational repression by 4E-T is crucial to maintain the prophase-I arrest in vertebrate oocytes.4E-T介导的翻译抑制对于维持脊椎动物卵母细胞减数分裂前期阻滞至关重要。
Nat Commun. 2025 Aug 28;16(1):8051. doi: 10.1038/s41467-025-62971-9.
3
Human eIF2A has a minimal role in translation initiation and in uORF-mediated translational control in HeLa cells.人类真核起始因子2A（eIF2A）在HeLa细胞的翻译起始以及上游开放阅读框（uORF）介导的翻译控制中作用极小。
Elife. 2025 Jul 2;14:RP105311. doi: 10.7554/eLife.105311.
4
Insights into Noncanonical and Diversified Functions of ABCF1: From Health to Disease.ABCF1的非规范和多样化功能洞察：从健康到疾病
J Mol Biol. 2025 Jun 11;437(17):169286. doi: 10.1016/j.jmb.2025.169286.
5
Translation elongation: measurements and applications.翻译延伸：测量与应用
RNA Biol. 2025 Dec;22(1):1-10. doi: 10.1080/15476286.2025.2504727. Epub 2025 May 16.
6
Emerging clinical and research approaches in targeted therapies for high-risk neuroblastoma.高危神经母细胞瘤靶向治疗中的新兴临床与研究方法。
Front Oncol. 2025 Mar 4;15:1553511. doi: 10.3389/fonc.2025.1553511. eCollection 2025.
7
Polysome profiling is an extensible tool for the analysis of bulk protein synthesis, ribosome biogenesis, and the specific steps in translation.多核糖体谱分析是一种用于分析整体蛋白质合成、核糖体生物发生及翻译特定步骤的可扩展工具。
Mol Biol Cell. 2025 Apr 1;36(4):mr2. doi: 10.1091/mbc.E24-08-0341. Epub 2025 Mar 5.
8
Maintenance of p-eIF2α levels by the eIF2B complex is vital for colorectal cancer.真核起始因子2B（eIF2B）复合体维持磷酸化真核起始因子2α（p-eIF2α）水平对结直肠癌至关重要。
EMBO J. 2025 Apr;44(7):2075-2105. doi: 10.1038/s44318-025-00381-9. Epub 2025 Feb 27.
9
eIF3d and eIF4G2 mediate an alternative mechanism of cap-dependent but eIF4E-independent translation initiation.真核生物翻译起始因子3d（eIF3d）和真核生物翻译起始因子4G2（eIF4G2）介导一种不依赖真核生物翻译起始因子4E（eIF4E）但依赖帽子结构的翻译起始替代机制。
J Biol Chem. 2025 Apr;301(4):108317. doi: 10.1016/j.jbc.2025.108317. Epub 2025 Feb 17.
10
Circadian clock control of interactions between eIF2α kinase CPC-3 and GCN1 with ribosomes regulates rhythmic translation initiation.昼夜节律钟对真核起始因子2α激酶CPC-3和GCN1与核糖体之间相互作用的调控可调节节律性翻译起始。
Proc Natl Acad Sci U S A. 2025 Feb 11;122(6):e2411916122. doi: 10.1073/pnas.2411916122. Epub 2025 Feb 4.
本文引用的文献
1
Specific domains in yeast translation initiation factor eIF4G strongly bias RNA unwinding activity of the eIF4F complex toward duplexes with 5'-overhangs.酵母翻译起始因子 eIF4G 的特定结构域强烈偏向于 eIF4F 复合物将具有 5'-突出的双链体进行 RNA 解链。
J Biol Chem. 2012 Jun 8;287(24):20301-12. doi: 10.1074/jbc.M112.347278. Epub 2012 Mar 30.
2
Structure of the ternary initiation complex aIF2-GDPNP-methionylated initiator tRNA.三元起始复合物 aIF2-GDPNP-甲硫氨酸起始 tRNA 的结构。
Nat Struct Mol Biol. 2012 Mar 25;19(4):450-4. doi: 10.1038/nsmb.2259.
3
Stringency of start codon selection modulates autoregulation of translation initiation factor eIF5.起始密码子选择的严格性调节翻译起始因子 eIF5 的自动调控。
Nucleic Acids Res. 2012 Apr;40(7):2898-906. doi: 10.1093/nar/gkr1192. Epub 2011 Dec 7.
4
Functional reconstitution of human eukaryotic translation initiation factor 3 (eIF3).人类真核翻译起始因子 3（eIF3）的功能重建。
Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20473-8. doi: 10.1073/pnas.1116821108. Epub 2011 Dec 1.
5
The structure of the eukaryotic ribosome at 3.0 Å resolution.真核生物核糖体的 3.0 Å 分辨率结构。
Science. 2011 Dec 16;334(6062):1524-9. doi: 10.1126/science.1212642. Epub 2011 Nov 17.
6
Initiation factor eIF2γ promotes eIF2-GTP-Met-tRNAi(Met) ternary complex binding to the 40S ribosome.起始因子 eIF2γ 促进 eIF2-GTP-Met-tRNAi(Met) 三元复合物与 40S 核糖体结合。
Nat Struct Mol Biol. 2011 Oct 16;18(11):1227-34. doi: 10.1038/nsmb.2133.
7
The human translation initiation multi-factor complex promotes methionyl-tRNAi binding to the 40S ribosomal subunit.人类翻译起始多因素复合物促进甲硫氨酰-tRNAi 结合到 40S 核糖体亚基。
Nucleic Acids Res. 2012 Jan;40(2):905-13. doi: 10.1093/nar/gkr772. Epub 2011 Sep 22.
8
Functional elements in initiation factors 1, 1A, and 2β discriminate against poor AUG context and non-AUG start codons.起始因子 1、1A 和 2β 中的功能元件可区分不良 AUG 序列和非 AUG 起始密码子。
Mol Cell Biol. 2011 Dec;31(23):4814-31. doi: 10.1128/MCB.05819-11. Epub 2011 Sep 19.
9
The DEAD-box protein Ded1 modulates translation by the formation and resolution of an eIF4F-mRNA complex.DEAD -box 蛋白 Ded1 通过形成和解离 eIF4F-mRNA 复合物来调节翻译。
Mol Cell. 2011 Sep 16;43(6):962-72. doi: 10.1016/j.molcel.2011.08.008.
10
Molecular mechanism of scanning and start codon selection in eukaryotes.真核生物扫描和起始密码子选择的分子机制。
Microbiol Mol Biol Rev. 2011 Sep;75(3):434-67, first page of table of contents. doi: 10.1128/MMBR.00008-11.
Zotero 插件