• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

翻译以依赖于密码子的方式影响人类细胞中的 mRNA 稳定性。

Translation affects mRNA stability in a codon-dependent manner in human cells.

机构信息

Stowers Institute for Medical Research, Kansas City, United States.

出版信息

Elife. 2019 Apr 23;8:e45396. doi: 10.7554/eLife.45396.

DOI:10.7554/eLife.45396
PMID:31012849
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6529216/
Abstract

mRNA translation decodes nucleotide into amino acid sequences. However, translation has also been shown to affect mRNA stability depending on codon composition in model organisms, although universality of this mechanism remains unclear. Here, using three independent approaches to measure exogenous and endogenous mRNA decay, we define which codons are associated with stable or unstable mRNAs in human cells. We demonstrate that the regulatory information affecting mRNA stability is encoded in codons and not in nucleotides. Stabilizing codons tend to be associated with higher tRNA levels and higher charged/total tRNA ratios. While mRNAs enriched in destabilizing codons tend to possess shorter poly(A)-tails, the poly(A)-tail is not required for the codon-mediated mRNA stability. This mechanism depends on translation; however, the number of ribosome loads into a mRNA modulates the codon-mediated effects on gene expression. This work provides definitive evidence that translation strongly affects mRNA stability in a codon-dependent manner in human cells.

摘要

mRNA 翻译将核苷酸解码为氨基酸序列。然而，在模式生物中，已有研究表明翻译也会影响 mRNA 的稳定性，取决于密码子组成，尽管该机制的普遍性尚不清楚。在这里，我们使用三种独立的方法来测量外源性和内源性 mRNA 的降解，以确定哪些密码子与人细胞中稳定或不稳定的 mRNA 相关。我们证明，影响 mRNA 稳定性的调节信息编码在密码子中，而不是在核苷酸中。稳定的密码子往往与更高的 tRNA 水平和更高的电荷/总 tRNA 比值相关。虽然富含不稳定密码子的 mRNA 往往具有较短的 poly(A)-尾，但 poly(A)-尾不是密码子介导的 mRNA 稳定性所必需的。该机制依赖于翻译；然而，核糖体进入 mRNA 的数量调节了密码子对基因表达的影响。这项工作提供了确凿的证据，证明在人类细胞中，翻译以依赖于密码子的方式强烈影响 mRNA 的稳定性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/080560130b85/elife-45396-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/e84ab2830a90/elife-45396-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/27ee462abab7/elife-45396-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/d4a81dda95c8/elife-45396-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/086b9401c3d5/elife-45396-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/0061039089e0/elife-45396-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/797fda97e463/elife-45396-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/6c09249b6330/elife-45396-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/6fa6c6d9148e/elife-45396-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/4cb72bcc47bd/elife-45396-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/b6f0ee9e2f79/elife-45396-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/080560130b85/elife-45396-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/e84ab2830a90/elife-45396-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/27ee462abab7/elife-45396-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/d4a81dda95c8/elife-45396-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/086b9401c3d5/elife-45396-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/0061039089e0/elife-45396-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/797fda97e463/elife-45396-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/6c09249b6330/elife-45396-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/6fa6c6d9148e/elife-45396-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/4cb72bcc47bd/elife-45396-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/b6f0ee9e2f79/elife-45396-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6449/6529216/080560130b85/elife-45396-fig6.jpg

相似文献

1
Translation affects mRNA stability in a codon-dependent manner in human cells.翻译以依赖于密码子的方式影响人类细胞中的 mRNA 稳定性。
Elife. 2019 Apr 23;8:e45396. doi: 10.7554/eLife.45396.
2
Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition.密码子特性在母源-合子转变过程中调节mRNA稳定性和翻译效率。
EMBO J. 2016 Oct 4;35(19):2087-2103. doi: 10.15252/embj.201694699. Epub 2016 Jul 19.
3
Translation and mRNA Stability Control.翻译与 mRNA 稳定性控制。
Annu Rev Biochem. 2023 Jun 20;92:227-245. doi: 10.1146/annurev-biochem-052621-091808. Epub 2023 Mar 31.
4
Codon optimality, bias and usage in translation and mRNA decay.密码子优化、偏性及其在翻译和mRNA降解中的使用
Nat Rev Mol Cell Biol. 2018 Jan;19(1):20-30. doi: 10.1038/nrm.2017.91. Epub 2017 Oct 11.
5
Ribosome slowdown triggers codon-mediated mRNA decay independently of ribosome quality control.核糖体减速独立于核糖体质量控制触发密码子介导的 mRNA 衰变。
EMBO J. 2022 Mar 1;41(5):e109256. doi: 10.15252/embj.2021109256. Epub 2022 Jan 18.
6
Codon optimality is a major determinant of mRNA stability.密码子最优性是信使核糖核酸稳定性的主要决定因素。
Cell. 2015 Mar 12;160(6):1111-24. doi: 10.1016/j.cell.2015.02.029.
7
Translation elongation and mRNA stability are coupled through the ribosomal A-site.通过核糖体 A 位，翻译延伸和 mRNA 稳定性被偶联在一起。
RNA. 2018 Oct;24(10):1377-1389. doi: 10.1261/rna.066787.118. Epub 2018 Jul 11.
8
Crosstalk between codon optimality and cis-regulatory elements dictates mRNA stability.密码子优化和顺式调控元件之间的串扰决定了 mRNA 的稳定性。
Genome Biol. 2021 Jan 5;22(1):14. doi: 10.1186/s13059-020-02251-5.
9
Geneticin reduces mRNA stability.遗传霉素降低 mRNA 稳定性。
PLoS One. 2022 Jul 28;17(7):e0272058. doi: 10.1371/journal.pone.0272058. eCollection 2022.
10
The DEAD-Box Protein Dhh1p Couples mRNA Decay and Translation by Monitoring Codon Optimality.DEAD盒蛋白Dhh1p通过监测密码子优化来耦合mRNA衰变与翻译。
Cell. 2016 Sep 22;167(1):122-132.e9. doi: 10.1016/j.cell.2016.08.053. Epub 2016 Sep 15.

引用本文的文献

1
Genetic variants affecting RNA stability influence complex traits and disease risk.影响RNA稳定性的基因变异会影响复杂性状和疾病风险。
Nat Genet. 2025 Sep 5. doi: 10.1038/s41588-025-02326-8.
2
Chemically modified tRNA enhances the translation capacity of mRNA rich in cognate codons.化学修饰的转运RNA增强了富含同源密码子的信使RNA的翻译能力。
Nat Commun. 2025 Aug 22;16(1):7825. doi: 10.1038/s41467-025-62981-7.
3
Quantitative modeling of mRNA degradation reveals tempo-dependent mRNA clearance in early embryos.mRNA降解的定量建模揭示了早期胚胎中与时间相关的mRNA清除情况。

本文引用的文献

1
Extensive Structural Differences of Closely Related 3' mRNA Isoforms: Links to Pab1 Binding and mRNA Stability.密切相关的3' mRNA异构体的广泛结构差异：与Pab1结合及mRNA稳定性的联系
Mol Cell. 2018 Dec 6;72(5):849-861.e6. doi: 10.1016/j.molcel.2018.08.044. Epub 2018 Oct 11.
2
Cells alter their tRNA abundance to selectively regulate protein synthesis during stress conditions.细胞改变其 tRNA 丰度以选择性地调节应激条件下的蛋白质合成。
Sci Signal. 2018 Sep 4;11(546):eaat6409. doi: 10.1126/scisignal.aat6409.
3
Repertoires of tRNAs: The Couplers of Genomics and Proteomics.
Nucleic Acids Res. 2025 Jul 19;53(14). doi: 10.1093/nar/gkaf737.
4
Predicting the translation efficiency of messenger RNA in mammalian cells.预测哺乳动物细胞中信使核糖核酸的翻译效率。
Nat Biotechnol. 2025 Jul 25. doi: 10.1038/s41587-025-02712-x.
5
A generalized and efficient approach for complete mRNA design improves translation, stability and specificity.一种用于完整mRNA设计的通用且高效的方法可提高翻译效率、稳定性和特异性。
bioRxiv. 2025 Jun 17:2025.06.17.659751. doi: 10.1101/2025.06.17.659751.
6
Macroevolutionary changes in natural selection on codon usage reflect evolution of the tRNA pool across a budding yeast subphylum.密码子使用上自然选择的宏观进化变化反映了整个芽殖酵母亚门tRNA库的进化。
Proc Natl Acad Sci U S A. 2025 Jul 8;122(27):e2419889122. doi: 10.1073/pnas.2419889122. Epub 2025 Jul 1.
7
The quantitative impact of 3'UTRs on gene expression.3'非翻译区对基因表达的定量影响。
Nucleic Acids Res. 2025 Jun 20;53(12). doi: 10.1093/nar/gkaf568.
8
Translational buffering tunes gene expression in mouse and human.翻译缓冲调节小鼠和人类的基因表达。
bioRxiv. 2025 May 21:2025.05.16.654561. doi: 10.1101/2025.05.16.654561.
9
Single-molecule direct RNA sequencing reveals the shaping of epitranscriptome across multiple species.单分子直接RNA测序揭示了多个物种中表观转录组的形成。
Nat Commun. 2025 Jun 2;16(1):5119. doi: 10.1038/s41467-025-60447-4.
10
mRNAdesigner: an integrated web server for optimizing mRNA design and protein translation in eukaryotes.mRNA设计器：用于优化真核生物中mRNA设计和蛋白质翻译的集成网络服务器。
Nucleic Acids Res. 2025 Jul 7;53(W1):W415-W426. doi: 10.1093/nar/gkaf410.
tRNA 库：基因组学和蛋白质组学的耦合器。
Annu Rev Cell Dev Biol. 2018 Oct 6;34:239-264. doi: 10.1146/annurev-cellbio-100617-062754. Epub 2018 Aug 20.
4
Attenuated Codon Optimality Contributes to Neural-Specific mRNA Decay in Drosophila.衰减密码子优化有助于果蝇神经特异性 mRNA 衰减。
Cell Rep. 2018 Aug 14;24(7):1704-1712. doi: 10.1016/j.celrep.2018.07.039.
5
Poor codon optimality as a signal to degrade transcripts with frameshifts.密码子优化性差作为一种信号，用于降解发生移码的转录本。
Transcription. 2018;9(5):327-333. doi: 10.1080/21541264.2018.1511676. Epub 2018 Aug 28.
6
Translation elongation and mRNA stability are coupled through the ribosomal A-site.通过核糖体 A 位，翻译延伸和 mRNA 稳定性被偶联在一起。
RNA. 2018 Oct;24(10):1377-1389. doi: 10.1261/rna.066787.118. Epub 2018 Jul 11.
7
mRNA Deadenylation Is Coupled to Translation Rates by the Differential Activities of Ccr4-Not Nucleases.mRNA 去腺苷酸化通过 Ccr4-Not 核酸酶的不同活性与翻译速率偶联。
Mol Cell. 2018 Jun 21;70(6):1089-1100.e8. doi: 10.1016/j.molcel.2018.05.033.
8
Codon usage of highly expressed genes affects proteome-wide translation efficiency.高表达基因的密码子使用影响蛋白质组范围的翻译效率。
Proc Natl Acad Sci U S A. 2018 May 22;115(21):E4940-E4949. doi: 10.1073/pnas.1719375115. Epub 2018 May 7.
9
Codon usage bias controls mRNA and protein abundance in trypanosomatids.密码子使用偏性控制着动质体中的 mRNA 和蛋白质丰度。
Elife. 2018 Mar 15;7:e32496. doi: 10.7554/eLife.32496.
10
Codon choice directs constitutive mRNA levels in trypanosomes.密码子选择指导锥虫中组成型 mRNA 水平。
Elife. 2018 Mar 15;7:e32467. doi: 10.7554/eLife.32467.