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翻译延伸抑制剂稳定特定的短寿命转录本。

Translation elongation inhibitors stabilize select short-lived transcripts.

机构信息

Johns Hopkins University School of Medicine, Department of Molecular Biology & Genetics, Baltimore, Maryland 21205, USA.

Johns Hopkins University School of Medicine, Department of Molecular Biology & Genetics, Baltimore, Maryland 21205, USA

出版信息

RNA. 2024 Nov 18;30(12):1572-1585. doi: 10.1261/rna.080138.124.


DOI:10.1261/rna.080138.124
PMID:39293933
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11571809/
Abstract

Translation elongation inhibitors are commonly used to study different cellular processes. Yet, their specific impact on transcription and mRNA decay has not been thoroughly assessed. Here, we use TimeLapse sequencing to investigate how translational stress impacts mRNA dynamics in human cells. Our results reveal that a distinct group of transcripts is stabilized in response to the translation elongation inhibitor emetine. These stabilized mRNAs are short-lived at steady state, and many of them encode C2H2 zinc finger proteins. The codon usage of these stabilized transcripts is suboptimal compared to other expressed transcripts, including other short-lived mRNAs that are not stabilized after emetine treatment. Finally, we show that stabilization of these transcripts is independent of ribosome quality control factors and signaling pathways activated by ribosome collisions. Our data describe a group of short-lived transcripts whose degradation is particularly sensitive to the inhibition of translation elongation.

摘要

翻译延伸抑制剂常用于研究不同的细胞过程。然而,它们对转录和 mRNA 降解的具体影响尚未得到彻底评估。在这里,我们使用延时测序来研究翻译应激如何影响人类细胞中的 mRNA 动态。我们的结果表明,一组独特的转录本在翻译延伸抑制剂依美丁的作用下稳定下来。这些稳定的 mRNA 在稳定状态下寿命较短,其中许多编码 C2H2 锌指蛋白。与其他表达的转录本相比,这些稳定的转录本的密码子使用情况不理想,包括其他在依美丁处理后不会稳定的短寿命 mRNA。最后,我们表明这些转录本的稳定与核糖体质量控制因子和由核糖体碰撞激活的信号通路无关。我们的数据描述了一组短寿命的转录本,其降解对翻译延伸的抑制特别敏感。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/11571809/e1f8a3c31140/1572f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/11571809/d15fbc37530a/1572f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/11571809/ed4f5164e0ab/1572f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/11571809/b2b2826429ad/1572f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/11571809/f8fb5cfe409a/1572f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/11571809/e1f8a3c31140/1572f05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/11571809/d15fbc37530a/1572f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/11571809/ed4f5164e0ab/1572f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/11571809/b2b2826429ad/1572f03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/11571809/f8fb5cfe409a/1572f04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/11571809/e1f8a3c31140/1572f05.jpg

相似文献

[1]
Translation elongation inhibitors stabilize select short-lived transcripts.

RNA. 2024-11-18

[2]
Quantification of elongation stalls and impact on gene expression in yeast.

RNA. 2023-12

[3]
Chemical modifications to mRNA nucleobases impact translation elongation and termination.

Biophys Chem. 2022-6

[4]
Codon usage regulates protein structure and function by affecting translation elongation speed in Drosophila cells.

Nucleic Acids Res. 2017-8-21

[5]
The DEAD-Box Protein Dhh1p Couples mRNA Decay and Translation by Monitoring Codon Optimality.

Cell. 2016-9-22

[6]
The ribosome in action: Tuning of translational efficiency and protein folding.

Protein Sci. 2016-8

[7]
Translation elongation and mRNA stability are coupled through the ribosomal A-site.

RNA. 2018-7-11

[8]
Codon optimality-mediated mRNA degradation: Linking translational elongation to mRNA stability.

Mol Cell. 2022-4-21

[9]
Distinct stages of the translation elongation cycle revealed by sequencing ribosome-protected mRNA fragments.

Elife. 2014-5-9

[10]
Translation inhibitors stabilize Escherichia coli mRNAs independently of ribosome protection.

Proc Natl Acad Sci U S A. 1998-5-26

引用本文的文献

[1]
Global inhibition of deadenylation stabilizes the transcriptome in mitotic cells.

bioRxiv. 2025-7-22

[2]
Translation elongation: measurements and applications.

RNA Biol. 2025-12

[3]
tRNA modifications tune mA-dependent mRNA decay.

Cell. 2025-7-10

本文引用的文献

[1]
Transposable elements drive the evolution of metazoan zinc finger genes.

Genome Res. 2023-8

[2]
bakR: uncovering differential RNA synthesis and degradation kinetics transcriptome-wide with Bayesian hierarchical modeling.

RNA. 2023-7

[3]
iCodon customizes gene expression based on the codon composition.

Sci Rep. 2022-7-15

[4]
Ribosome collisions induce mRNA cleavage and ribosome rescue in bacteria.

Nature. 2022-3

[5]
Unresolved stalled ribosome complexes restrict cell-cycle progression after genotoxic stress.

Mol Cell. 2022-4-21

[6]
Ribosome states signal RNA quality control.

Mol Cell. 2021-4-1

[7]
A Quick Guide to Small-Molecule Inhibitors of Eukaryotic Protein Synthesis.

Biochemistry (Mosc). 2020-11

[8]
EDF1 coordinates cellular responses to ribosome collisions.

Elife. 2020-8-3

[9]
GIGYF2 and 4EHP Inhibit Translation Initiation of Defective Messenger RNAs to Assist Ribosome-Associated Quality Control.

Mol Cell. 2020-7-28

[10]
Ribosome collisions trigger cis-acting feedback inhibition of translation initiation.

Elife. 2020-7-13

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