TModBase: Deciphering the Landscape of TRNA Modifications and Their Dynamic Changes from Epitranscriptome Data

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2022 Nov 21

PMID 36408909

Authors

Hao-Tian Lei

Zhang-Hao Wang

Bin Li

Yang Sun

Shi-Qiang Mei

Jian-Hua Yang

Liang-Hu Qu

Ling-Ling Zheng

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

NAIL-MS reveals tRNA and rRNA hypomodification as a consequence of 5-fluorouracil treatment.

Berg M, Li C, Kaiser S Nucleic Acids Res. 2025; 53(4).

PMID: 39997220 PMC: 11851100. DOI: 10.1093/nar/gkaf090.

Altered tRNA expression profile associated with codon-specific proteomic changes in the suicide brain.

Blaze J, Chen S, Heissel S, Alwaseem H, Landinez Macias M, Peter C Mol Psychiatry. 2025; .

PMID: 39809846 DOI: 10.1038/s41380-025-02891-8.

tRNA and tsRNA: From Heterogeneity to Multifaceted Regulators.

Li Y, Yu Z, Jiang W, Lyu X, Guo A, Sun X Biomolecules. 2024; 14(10).

PMID: 39456272 PMC: 11506809. DOI: 10.3390/biom14101340.

tRNA expression and modification landscapes, and their dynamics during zebrafish embryo development.

Rappol T, Waldl M, Chugunova A, Hofacker I, Pauli A, Vilardo E Nucleic Acids Res. 2024; 52(17):10575-10594.

PMID: 38989621 PMC: 11417395. DOI: 10.1093/nar/gkae595.

[Advances in mapping analysis of ribonucleic acid modifications through sequencing].

Xiong J, Feng T, Yuan B Se Pu. 2024; 42(7):632-645.

PMID: 38966972 PMC: 11224946. DOI: 10.3724/SP.J.1123.2023.12025.

References

Begley U, Dyavaiah M, Patil A, Rooney J, DiRenzo D, Young C . Trm9-catalyzed tRNA modifications link translation to the DNA damage response. Mol Cell. 2007; 28(5):860-70. PMC: 2211415. DOI: 10.1016/j.molcel.2007.09.021. View

Pereira M, Francisco S, Varanda A, Santos M, Santos M, Soares A . Impact of tRNA Modifications and tRNA-Modifying Enzymes on Proteostasis and Human Disease. Int J Mol Sci. 2018; 19(12). PMC: 6321623. DOI: 10.3390/ijms19123738. View

SCHMIDT P, Sierzputowska-Gracz H, Agris P . Internal motions in yeast phenylalanine transfer RNA from 13C NMR relaxation rates of modified base methyl groups: a model-free approach. Biochemistry. 1987; 26(26):8529-34. DOI: 10.1021/bi00400a006. View

Mace K, Gillet R . Origins of tmRNA: the missing link in the birth of protein synthesis?. Nucleic Acids Res. 2016; 44(17):8041-51. PMC: 5041485. DOI: 10.1093/nar/gkw693. View

Shurtleff M, Yao J, Qin Y, Nottingham R, Temoche-Diaz M, Schekman R . Broad role for YBX1 in defining the small noncoding RNA composition of exosomes. Proc Natl Acad Sci U S A. 2017; 114(43):E8987-E8995. PMC: 5663387. DOI: 10.1073/pnas.1712108114. View

Thomas N, Poodari V, Jain M, Olsen H, Akeson M, Abu-Shumays R . Direct Nanopore Sequencing of Individual Full Length tRNA Strands. ACS Nano. 2021; 15(10):16642-16653. PMC: 10189790. DOI: 10.1021/acsnano.1c06488. View

Suzuki T . The expanding world of tRNA modifications and their disease relevance. Nat Rev Mol Cell Biol. 2021; 22(6):375-392. DOI: 10.1038/s41580-021-00342-0. View

Pan T . Modifications and functional genomics of human transfer RNA. Cell Res. 2018; 28(4):395-404. PMC: 5939049. DOI: 10.1038/s41422-018-0013-y. View

Tucker J, Schaller A, Willis I, Glaunsinger B . Alteration of the Premature tRNA Landscape by Gammaherpesvirus Infection. mBio. 2020; 11(6). PMC: 7773990. DOI: 10.1128/mBio.02664-20. View

10.

Xuan J, Sun W, Lin P, Zhou K, Liu S, Zheng L . RMBase v2.0: deciphering the map of RNA modifications from epitranscriptome sequencing data. Nucleic Acids Res. 2017; 46(D1):D327-D334. PMC: 5753293. DOI: 10.1093/nar/gkx934. View

11.

Tuorto F, Liebers R, Musch T, Schaefer M, Hofmann S, Kellner S . RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis. Nat Struct Mol Biol. 2012; 19(9):900-5. DOI: 10.1038/nsmb.2357. View

12.

Workman R, Tang A, Tang P, Jain M, Tyson J, Razaghi R . Nanopore native RNA sequencing of a human poly(A) transcriptome. Nat Methods. 2019; 16(12):1297-1305. PMC: 7768885. DOI: 10.1038/s41592-019-0617-2. View

13.

Farias S, Jose M . Transfer RNA: The molecular demiurge in the origin of biological systems. Prog Biophys Mol Biol. 2020; 153:28-34. DOI: 10.1016/j.pbiomolbio.2020.02.006. View

14.

Squires J, Patel H, Nousch M, Sibbritt T, Humphreys D, Parker B . Widespread occurrence of 5-methylcytosine in human coding and non-coding RNA. Nucleic Acids Res. 2012; 40(11):5023-33. PMC: 3367185. DOI: 10.1093/nar/gks144. View

15.

Boccaletto P, Stefaniak F, Ray A, Cappannini A, Mukherjee S, Purta E . MODOMICS: a database of RNA modification pathways. 2021 update. Nucleic Acids Res. 2021; 50(D1):D231-D235. PMC: 8728126. DOI: 10.1093/nar/gkab1083. View

16.

Garalde D, Snell E, Jachimowicz D, Sipos B, Lloyd J, Bruce M . Highly parallel direct RNA sequencing on an array of nanopores. Nat Methods. 2018; 15(3):201-206. DOI: 10.1038/nmeth.4577. View

17.

Zheng G, Qin Y, Clark W, Dai Q, Yi C, He C . Efficient and quantitative high-throughput tRNA sequencing. Nat Methods. 2015; 12(9):835-837. PMC: 4624326. DOI: 10.1038/nmeth.3478. View

18.

Cantara W, Bilbille Y, Kim J, Kaiser R, Leszczynska G, Malkiewicz A . Modifications modulate anticodon loop dynamics and codon recognition of E. coli tRNA(Arg1,2). J Mol Biol. 2012; 416(4):579-97. DOI: 10.1016/j.jmb.2011.12.054. View

19.

Cozen A, Quartley E, Holmes A, Hrabeta-Robinson E, Phizicky E, Lowe T . ARM-seq: AlkB-facilitated RNA methylation sequencing reveals a complex landscape of modified tRNA fragments. Nat Methods. 2015; 12(9):879-84. PMC: 4553111. DOI: 10.1038/nmeth.3508. View

20.

Chionh Y, McBee M, Babu I, Hia F, Lin W, Zhao W . tRNA-mediated codon-biased translation in mycobacterial hypoxic persistence. Nat Commun. 2016; 7:13302. PMC: 5114619. DOI: 10.1038/ncomms13302. View