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无终止密码子的翻译终止。

Translational termination without a stop codon.

作者信息

James Nathan R, Brown Alan, Gordiyenko Yuliya, Ramakrishnan V

机构信息

Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.

出版信息

Science. 2016 Dec 16;354(6318):1437-1440. doi: 10.1126/science.aai9127. Epub 2016 Dec 1.

DOI:10.1126/science.aai9127
PMID:27934701
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5351859/
Abstract

Ribosomes stall when they encounter the end of messenger RNA (mRNA) without an in-frame stop codon. In bacteria, these "nonstop" complexes can be rescued by alternative ribosome-rescue factor A (ArfA). We used electron cryomicroscopy to determine structures of ArfA bound to the ribosome with 3'-truncated mRNA, at resolutions ranging from 3.0 to 3.4 angstroms. ArfA binds within the ribosomal mRNA channel and substitutes for the absent stop codon in the A site by specifically recruiting release factor 2 (RF2), initially in a compact preaccommodated state. A similar conformation of RF2 may occur on stop codons, suggesting a general mechanism for release-factor-mediated translational termination in which a conformational switch leads to peptide release only when the appropriate signal is present in the A site.

摘要

当核糖体遇到没有框内终止密码子的信使核糖核酸(mRNA)末端时,就会发生停滞。在细菌中,这些“无义”复合物可被替代核糖体拯救因子A(ArfA)拯救。我们使用冷冻电子显微镜在3.0至3.4埃的分辨率下确定了ArfA与带有3'端截短mRNA的核糖体结合的结构。ArfA结合在核糖体mRNA通道内,并通过特异性招募释放因子2(RF2)来替代A位点中缺失的终止密码子,最初RF2处于紧密的预适应状态。RF2在终止密码子上可能会出现类似的构象,这表明释放因子介导的翻译终止存在一种普遍机制,即仅当A位点存在适当信号时,构象转换才会导致肽段释放。

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Translational termination without a stop codon.无终止密码子的翻译终止。
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2
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本文引用的文献

1
Ribosome Induces a Closed to Open Conformational Change in Release Factor 1.核糖体诱导释放因子1发生从封闭构象到开放构象的变化。
J Mol Biol. 2016 Mar 27;428(6):1333-1344. doi: 10.1016/j.jmb.2016.01.021. Epub 2016 Jan 29.
2
Peptide release promoted by methylated RF2 and ArfA in nonstop translation is achieved by an induced-fit mechanism.在无义介导的翻译中,甲基化的RF2和ArfA促进的肽释放是通过诱导契合机制实现的。
RNA. 2016 Jan;22(1):49-60. doi: 10.1261/rna.053082.115. Epub 2015 Nov 9.
3
Mechanisms of ribosome rescue in bacteria.细菌中核糖体救援的机制。
在大肠杆菌中,停滞核糖体拯救因子根据抗生素类型发挥不同作用。
NPJ Antimicrob Resist. 2024 Sep 2;2(1):22. doi: 10.1038/s44259-024-00039-2.
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In situ architecture of a nucleoid-associated biomolecular co-condensate that regulates bacterial cell division.一种调节细菌细胞分裂的类核相关生物分子共凝聚物的原位结构。
Proc Natl Acad Sci U S A. 2025 Jan 7;122(1):e2419610121. doi: 10.1073/pnas.2419610121. Epub 2024 Dec 31.
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Mechanistic insights into the alternative ribosome recycling by HflXr.关于HflXr介导的替代性核糖体循环的机制性见解。
Nucleic Acids Res. 2024 Apr 24;52(7):4053-4066. doi: 10.1093/nar/gkae128.
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A trailing ribosome speeds up RNA polymerase at the expense of transcript fidelity via force and allostery.尾随核糖体通过力和变构作用提高 RNA 聚合酶的速度,但其代价是转录保真度。
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Prophage excision switches the primary ribosome rescue pathway and rescue-associated gene regulations in Escherichia coli.噬菌体切除可改变大肠杆菌中主要核糖体拯救途径和拯救相关基因的调控。
Mol Microbiol. 2023 Jan;119(1):44-58. doi: 10.1111/mmi.15003. Epub 2022 Dec 5.
8
Sequential rescue and repair of stalled and damaged ribosome by bacterial PrfH and RtcB.细菌 PrfH 和 RtcB 对stalled 和 damaged ribosome 的顺序救援和修复。
Proc Natl Acad Sci U S A. 2022 Jul 19;119(29):e2202464119. doi: 10.1073/pnas.2202464119. Epub 2022 Jul 12.
9
Ribosome-associated quality-control mechanisms from bacteria to humans.核糖体相关质量控制机制:从细菌到人。
Mol Cell. 2022 Apr 21;82(8):1451-1466. doi: 10.1016/j.molcel.2022.03.038.
10
The Structural Dynamics of Translation.翻译的结构动力学。
Annu Rev Biochem. 2022 Jun 21;91:245-267. doi: 10.1146/annurev-biochem-071921-122857. Epub 2022 Mar 14.
Nat Rev Microbiol. 2015 May;13(5):285-97. doi: 10.1038/nrmicro3438. Epub 2015 Apr 13.
4
ArfA recognizes the lack of mRNA in the mRNA channel after RF2 binding for ribosome rescue.ArfA在RF2结合后识别mRNA通道中mRNA的缺失,以进行核糖体拯救。
Nucleic Acids Res. 2014 Dec 1;42(21):13339-52. doi: 10.1093/nar/gku1069. Epub 2014 Oct 29.
5
The task force that rescues stalled ribosomes in bacteria.负责救援细菌中停滞核糖体的工作组。
Trends Biochem Sci. 2013 Aug;38(8):403-11. doi: 10.1016/j.tibs.2013.06.002. Epub 2013 Jun 30.
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Structural basis of the translational elongation cycle.翻译:翻译的结构基础。
Annu Rev Biochem. 2013;82:203-36. doi: 10.1146/annurev-biochem-113009-092313.
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Small molecule inhibitors of trans-translation have broad-spectrum antibiotic activity.小分子转译抑制剂具有广谱抗生素活性。
Proc Natl Acad Sci U S A. 2013 Jun 18;110(25):10282-7. doi: 10.1073/pnas.1302816110. Epub 2013 Jun 3.
8
ArfA recruits RF2 into stalled ribosomes.ArfA 将 RF2 招募到stalled ribosomes 中。
J Mol Biol. 2012 Nov 2;423(4):624-31. doi: 10.1016/j.jmb.2012.08.007. Epub 2012 Aug 21.
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ArfA recruits release factor 2 to rescue stalled ribosomes by peptidyl-tRNA hydrolysis in Escherichia coli.ArfA 招募释放因子 2 通过肽酰-tRNA 水解在大肠杆菌中拯救停滞的核糖体。
Mol Microbiol. 2012 Oct;86(1):37-50. doi: 10.1111/j.1365-2958.2012.08190.x. Epub 2012 Aug 22.
10
Proteobacterial ArfA peptides are synthesized from non-stop messenger RNAs.细菌的 ArfA 肽是从无终止的信使 RNA 合成的。
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