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定量RNA假尿苷图谱揭示了通过植物核糖体RNA、转运RNA和信使RNA假尿苷化实现的多层翻译控制。

Quantitative RNA pseudouridine maps reveal multilayered translation control through plant rRNA, tRNA and mRNA pseudouridylation.

作者信息

Li Haoxuan, Wang Guanqun, Ye Chang, Zou Zhongyu, Jiang Bochen, Yang Fan, He Kayla, Ju Chengwei, Zhang Lisheng, Gao Boyang, Liu Shun, Chen Yanming, Zhang Jianhua, He Chuan

机构信息

Department of Chemistry, Department of Biochemistry and Molecular Biology, and Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL, USA.

Howard Hughes Medical Institute, Chicago, IL, USA.

出版信息

Nat Plants. 2025 Feb;11(2):234-247. doi: 10.1038/s41477-024-01894-7. Epub 2025 Jan 9.

DOI:10.1038/s41477-024-01894-7
PMID:39789092
Abstract

Pseudouridine (Ψ) is the most abundant RNA modification, yet studies of Ψ have been hindered by a lack of robust methods to profile comprehensive Ψ maps. Here we utilize bisulfite-induced deletion sequencing to generate transcriptome-wide Ψ maps at single-base resolution across various plant species. Integrating ribosomal RNA, transfer RNA and messenger RNA Ψ stoichiometry with mRNA abundance and polysome profiling data, we uncover a multilayered regulation of translation efficiency through Ψ modifications. rRNA pseudouridylation could globally control translation, although the effects vary at different rRNA Ψ sites. Ψ in the tRNA T-arm loop shows strong positive correlations between Ψ stoichiometry and the translation efficiency of their respective codons. We observed a general inverse correlation between Ψ level and mRNA stability, but a positive correlation with translation efficiency in Arabidopsis seedlings. In conclusion, our study provides critical resources for Ψ research in plants and proposes prevalent translation regulation through rRNA, tRNA and mRNA pseudouridylation.

摘要

假尿苷(Ψ)是最丰富的RNA修饰,但由于缺乏可靠的方法来绘制全面的Ψ图谱,对Ψ的研究受到了阻碍。在此,我们利用亚硫酸氢盐诱导的缺失测序技术,在单碱基分辨率下生成了多种植物物种的全转录组Ψ图谱。通过将核糖体RNA、转运RNA和信使RNA的Ψ化学计量与mRNA丰度及多聚核糖体分析数据相结合,我们揭示了通过Ψ修饰对翻译效率的多层次调控。核糖体RNA假尿苷化可以全局控制翻译,尽管在不同的核糖体RNA Ψ位点其影响有所不同。转运RNA T环中的Ψ在其化学计量与其各自密码子的翻译效率之间显示出强烈的正相关。我们观察到在拟南芥幼苗中,Ψ水平与mRNA稳定性之间普遍呈负相关,但与翻译效率呈正相关。总之,我们的研究为植物中Ψ的研究提供了关键资源,并提出了通过核糖体RNA、转运RNA和信使RNA假尿苷化进行普遍翻译调控的观点。

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本文引用的文献

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Modifications in the T arm of tRNA globally determine tRNA maturation, function, and cellular fitness.tRNA T 臂的改变全面决定 tRNA 的成熟、功能和细胞适应性。
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BID-seq for transcriptome-wide quantitative sequencing of mRNA pseudouridine at base resolution.用于全转录组范围碱基分辨率的mRNA假尿苷定量测序的BID-seq。
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Regulation of translation by ribosomal RNA pseudouridylation.
核糖体 RNA 假尿嘧啶核苷修饰调控翻译。
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Control of protein synthesis through mRNA pseudouridylation by dyskerin.通过核蛋白 dyskerin 对 mRNA 假尿嘧啶核苷修饰来控制蛋白质合成。
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Effect of mRNA/tRNA mutations on translation speed: Implications for human diseases.mRNA/tRNA 突变对翻译速度的影响:对人类疾病的启示。
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tRNA Modifications and Modifying Enzymes in Disease, the Potential Therapeutic Targets.tRNA 修饰与修饰酶在疾病中的作用:潜在的治疗靶点
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Quantitative sequencing using BID-seq uncovers abundant pseudouridines in mammalian mRNA at base resolution.BID-seq 定量测序技术在碱基分辨率水平上揭示了哺乳动物 mRNA 中的大量假尿嘧啶核苷。
Nat Biotechnol. 2023 Mar;41(3):344-354. doi: 10.1038/s41587-022-01505-w. Epub 2022 Oct 27.
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