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对mRNA核碱基的化学修饰会影响翻译延伸和终止。

Chemical modifications to mRNA nucleobases impact translation elongation and termination.

作者信息

Franco Monika K, Koutmou Kristin S

机构信息

Program in Chemical Biology, University of Michigan, USA.

Program in Chemical Biology, University of Michigan, USA; Department of Chemistry, University of Michigan, USA.

出版信息

Biophys Chem. 2022 Jun;285:106780. doi: 10.1016/j.bpc.2022.106780. Epub 2022 Feb 16.


DOI:10.1016/j.bpc.2022.106780
PMID:35313212
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9373004/
Abstract

Messenger RNAs (mRNAs) serve as blueprints for protein synthesis by the molecular machine the ribosome. The ribosome relies on hydrogen bonding interactions between adaptor aminoacyl-transfer RNA molecules and mRNAs to ensure the rapid and faithful translation of the genetic code into protein. There is a growing body of evidence suggesting that chemical modifications to mRNA nucleosides impact the speed and accuracy of protein synthesis by the ribosome. Modulations in translation rates have downstream effects beyond protein production, influencing protein folding and mRNA stability. Given the prevalence of such modifications in mRNA coding regions, it is imperative to understand the consequences of individual modifications on translation. In this review we present the current state of our knowledge regarding how individual mRNA modifications influence ribosome function. Our comprehensive comparison of the impacts of 16 different mRNA modifications on translation reveals that most modifications can alter the elongation step in the protein synthesis pathway. Additionally, we discuss the context dependence of these effects, highlighting the necessity of further study to uncover the rules that govern how any given chemical modification in an mRNA codon is read by the ribosome.

摘要

信使核糖核酸(mRNA)作为核糖体这一分子机器进行蛋白质合成的蓝图。核糖体依靠衔接子氨酰转运RNA分子与mRNA之间的氢键相互作用,以确保将遗传密码快速且准确地翻译成蛋白质。越来越多的证据表明,对mRNA核苷的化学修饰会影响核糖体进行蛋白质合成的速度和准确性。翻译速率的调节在蛋白质产生之外还具有下游效应,影响蛋白质折叠和mRNA稳定性。鉴于此类修饰在mRNA编码区普遍存在,了解单个修饰对翻译的影响至关重要。在本综述中,我们阐述了关于单个mRNA修饰如何影响核糖体功能的当前知识状态。我们对16种不同mRNA修饰对翻译的影响进行的全面比较表明,大多数修饰会改变蛋白质合成途径中的延伸步骤。此外,我们讨论了这些效应的背景依赖性,强调了进一步研究以揭示核糖体如何读取mRNA密码子中任何给定化学修饰的规则的必要性。

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Chemical modifications to mRNA nucleobases impact translation elongation and termination.

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[2]
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[3]
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[4]
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[8]
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[3]
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[4]
Probing enzyme-dependent pseudouridylation using direct RNA sequencing to assess epitranscriptome plasticity in a neuronal cell line.

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[5]
The ribosome as a platform to coordinate mRNA decay.

Nucleic Acids Res. 2025-2-8

[6]
Sequencing technologies to measure translation in single cells.

Nat Rev Mol Cell Biol. 2025-5

[7]
N1-Methylpseudouridine and pseudouridine modifications modulate mRNA decoding during translation.

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[8]
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[9]
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[10]
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本文引用的文献

[1]
mRNA and tRNA modification states influence ribosome speed and frame maintenance during poly(lysine) peptide synthesis.

J Biol Chem. 2022-6

[2]
scDART-seq reveals distinct mA signatures and mRNA methylation heterogeneity in single cells.

Mol Cell. 2022-2-17

[3]
Pseudouridine synthase 7 is an opportunistic enzyme that binds and modifies substrates with diverse sequences and structures.

Proc Natl Acad Sci U S A. 2022-1-25

[4]
Pseudouridine synthases modify human pre-mRNA co-transcriptionally and affect pre-mRNA processing.

Mol Cell. 2022-2-3

[5]
Membrane-dependent relief of translation elongation arrest on pseudouridine- and N1-methyl-pseudouridine-modified mRNAs.

Nucleic Acids Res. 2022-7-22

[6]
Transcription-wide mapping of dihydrouridine reveals that mRNA dihydrouridylation is required for meiotic chromosome segregation.

Mol Cell. 2022-1-20

[7]
Activity-based RNA-modifying enzyme probing reveals DUS3L-mediated dihydrouridylation.

Nat Chem Biol. 2021-11

[8]
Modifications in an Emergency: The Role of N1-Methylpseudouridine in COVID-19 Vaccines.

ACS Cent Sci. 2021-5-26

[9]
Detecting the epitranscriptome.

Wiley Interdiscip Rev RNA. 2021-11

[10]
Inosine in Biology and Disease.

Genes (Basel). 2021-4-19

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