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mRNA 多聚（A）尾长度对真核翻译阶段的影响。

The impact of mRNA poly(A) tail length on eukaryotic translation stages.

机构信息

Engelhardt Institute of Molecular Biology, the Russian Academy of Sciences, 119991 Moscow, Russia.

Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, the Russian Academy of Sciences, 119991 Moscow, Russia.

出版信息

Nucleic Acids Res. 2024 Jul 22;52(13):7792-7808. doi: 10.1093/nar/gkae510.

DOI:10.1093/nar/gkae510
PMID:38874498
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11260481/
Abstract

The poly(A) tail plays an important role in maintaining mRNA stability and influences translation efficiency via binding with PABP. However, the impact of poly(A) tail length on mRNA translation remains incompletely understood. This study explores the effects of poly(A) tail length on human translation. We determined the translation rates in cell lysates using mRNAs with different poly(A) tails. Cap-dependent translation was stimulated by the poly(A) tail, however, it was largely independent of poly(A) tail length, with an exception observed in the case of the 75 nt poly(A) tail. Conversely, cap-independent translation displayed a positive correlation with poly(A) tail length. Examination of translation stages uncovered the dependence of initiation and termination on the presence of the poly(A) tail, but the efficiency of initiation remained unaffected by poly(A) tail extension. Further study unveiled that increased binding of eRFs to the ribosome with the poly(A) tail extension induced more efficient hydrolysis of peptidyl-tRNA. Building upon these findings, we propose a crucial role for the 75 nt poly(A) tail in orchestrating the formation of a double closed-loop mRNA structure within human cells which couples the initiation and termination phases of translation.

摘要

多聚腺苷酸 (poly(A)) 尾巴在维持 mRNA 稳定性和通过与 PABP 结合影响翻译效率方面发挥着重要作用。然而，poly(A) 尾巴长度对 mRNA 翻译的影响仍不完全清楚。本研究探讨了 poly(A) 尾巴长度对人类翻译的影响。我们使用具有不同 poly(A) 尾巴的 mRNA 在细胞裂解物中测定翻译速率。Cap 依赖性翻译受到 poly(A) 尾巴的刺激，但在 75nt poly(A) 尾巴的情况下，它在很大程度上独立于 poly(A) 尾巴长度。相反，Cap 非依赖性翻译与 poly(A) 尾巴长度呈正相关。对翻译阶段的检查揭示了起始和终止对 poly(A) 尾巴存在的依赖性，但 poly(A) 尾巴延伸对起始效率没有影响。进一步的研究表明，eRFs 与 poly(A) 尾巴延伸的核糖体结合增加，导致肽酰-tRNA 的水解更有效。基于这些发现，我们提出 75nt poly(A) 尾巴在协调人类细胞内双闭环 mRNA 结构的形成中起着至关重要的作用，该结构将翻译的起始和终止阶段偶联起来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa9/11260481/7f89568ba9f5/gkae510fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa9/11260481/6f82d2bf57d8/gkae510figgra1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa9/11260481/4287c8b19fbe/gkae510fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa9/11260481/3f1abf1afdc6/gkae510fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa9/11260481/60ec5f453af5/gkae510fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa9/11260481/130cfecc00fd/gkae510fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa9/11260481/8d894ce5a6f3/gkae510fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa9/11260481/7f89568ba9f5/gkae510fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa9/11260481/6f82d2bf57d8/gkae510figgra1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa9/11260481/4287c8b19fbe/gkae510fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa9/11260481/3f1abf1afdc6/gkae510fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa9/11260481/60ec5f453af5/gkae510fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa9/11260481/130cfecc00fd/gkae510fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa9/11260481/8d894ce5a6f3/gkae510fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa9/11260481/7f89568ba9f5/gkae510fig6.jpg

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