MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, P.R. China.
Division of Biosciences, University College London, London WC1E 6BT, UK.
Nucleic Acids Res. 2023 Jan 6;51(D1):D315-D327. doi: 10.1093/nar/gkac1087.
tRNA molecules contain dense, abundant modifications that affect tRNA structure, stability, mRNA decoding and tsRNA formation. tRNA modifications and related enzymes are responsive to environmental cues and are associated with a range of physiological and pathological processes. However, there is a lack of resources that can be used to mine and analyse these dynamically changing tRNA modifications. In this study, we established tModBase (https://www.tmodbase.com/) for deciphering the landscape of tRNA modification profiles from epitranscriptome data. We analysed 103 datasets generated with second- and third-generation sequencing technologies and illustrated the misincorporation and termination signals of tRNA modification sites in ten species. We thus systematically demonstrate the modification profiles across different tissues/cell lines and summarize the characteristics of tRNA-associated human diseases. By integrating transcriptome data from 32 cancers, we developed novel tools for analysing the relationships between tRNA modifications and RNA modification enzymes, the expression of 1442 tRNA-derived small RNAs (tsRNAs), and 654 DNA variations. Our database will provide new insights into the features of tRNA modifications and the biological pathways in which they participate.
tRNA 分子含有丰富的密集修饰,这些修饰影响 tRNA 结构、稳定性、mRNA 解码和 tsRNA 形成。tRNA 修饰及其相关酶对环境信号有反应,并与一系列生理和病理过程有关。然而,目前缺乏可用于挖掘和分析这些动态变化的 tRNA 修饰的资源。在这项研究中,我们建立了 tModBase(https://www.tmodbase.com/),用于从转录组数据中破译 tRNA 修饰谱的全景。我们分析了 103 个基于第二代和第三代测序技术生成的数据集,并在十种物种中说明了 tRNA 修饰位点的误掺入和终止信号。因此,我们系统地展示了不同组织/细胞系中的修饰谱,并总结了与 tRNA 相关的人类疾病的特征。通过整合来自 32 种癌症的转录组数据,我们开发了新的工具来分析 tRNA 修饰与 RNA 修饰酶、1442 种 tRNA 衍生的小 RNA(tsRNA)和 654 种 DNA 变异之间的关系。我们的数据库将为 tRNA 修饰的特征以及它们参与的生物学途径提供新的见解。