TRNA Modifications and TRNA-derived Small RNAs: New Insights of TRNA in Human Disease

Overview

Journal Cell Biol Toxicol

Publisher Springer

Specialties Cell Biology
Toxicology

Date 2024 Sep 14

PMID 39276283

Authors

Di Wu

Xiuling Li

Faheem Ahmed Khan

Chenyang Yuan

Nuruliarizki Shinta Pandupuspitasari

Chunjie Huang

Fei Sun

Kaifeng Guan

Affiliations

Soon will be listed here.

Abstract

tRNAs are codon decoders that convert the transcriptome into the proteome. The field of tRNA research is excited by the increasing discovery of specific tRNA modifications that are installed at specific, evolutionarily conserved positions by a set of specialized tRNA-modifying enzymes and the biogenesis of tRNA-derived regulatory fragments (tsRNAs) which exhibit copious activities through multiple mechanisms. Dysregulation of tRNA modification usually has pathological consequences, a phenomenon referred to as "tRNA modopathy". Current evidence suggests that certain tRNA-modifying enzymes and tsRNAs may serve as promising diagnostic biomarkers and therapeutic targets, particularly for chemoresistant cancers. In this review, we discuss the latest discoveries that elucidate the molecular mechanisms underlying the functions of clinically relevant tRNA modifications and tsRNAs, with a focus on malignancies. We also discuss the therapeutic potential of tRNA/tsRNA-based therapies, aiming to provide insights for the development of innovative therapeutic strategies. Further efforts to unravel the complexities inherent in tRNA biology hold the promise of yielding better biomarkers for the diagnosis and prognosis of diseases, thereby advancing the development of precision medicine for health improvement.

Citing Articles

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References

Albers S, Allen E, Bharti N, Davyt M, Joshi D, Perez-Garcia C . Engineered tRNAs suppress nonsense mutations in cells and in vivo. Nature. 2023; 618(7966):842-848. PMC: 10284701. DOI: 10.1038/s41586-023-06133-1. View

Angelova M, Dimitrova D, Silva B, Marchand V, Jacquier C, Achour C . tRNA 2'-O-methylation by a duo of TRM7/FTSJ1 proteins modulates small RNA silencing in Drosophila. Nucleic Acids Res. 2020; 48(4):2050-2072. PMC: 7038984. DOI: 10.1093/nar/gkaa002. View

Balatti V, Rizzotto L, Miller C, Palamarchuk A, Fadda P, Pandolfo R . TCL1 targeting miR-3676 is codeleted with tumor protein p53 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A. 2015; 112(7):2169-74. PMC: 4343115. DOI: 10.1073/pnas.1500010112. View

Balatti V, Nigita G, Veneziano D, Drusco A, Stein G, Messier T . tsRNA signatures in cancer. Proc Natl Acad Sci U S A. 2017; 114(30):8071-8076. PMC: 5544330. DOI: 10.1073/pnas.1706908114. View

Barbieri I, Kouzarides T . Role of RNA modifications in cancer. Nat Rev Cancer. 2020; 20(6):303-322. DOI: 10.1038/s41568-020-0253-2. View

Baxter-Roshek J, Petrov A, Dinman J . Optimization of ribosome structure and function by rRNA base modification. PLoS One. 2007; 2(1):e174. PMC: 1766470. DOI: 10.1371/journal.pone.0000174. View

Behrens A, Rodschinka G, Nedialkova D . High-resolution quantitative profiling of tRNA abundance and modification status in eukaryotes by mim-tRNAseq. Mol Cell. 2021; 81(8):1802-1815.e7. PMC: 8062790. DOI: 10.1016/j.molcel.2021.01.028. View

Berg M, Brandl C . Transfer RNAs: diversity in form and function. RNA Biol. 2020; 18(3):316-339. PMC: 7954030. DOI: 10.1080/15476286.2020.1809197. View

Blanco S, Dietmann S, Flores J, Hussain S, Kutter C, Humphreys P . Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. EMBO J. 2014; 33(18):2020-39. PMC: 4195770. DOI: 10.15252/embj.201489282. View

10.

Blanco S, Bandiera R, Popis M, Hussain S, Lombard P, Aleksic J . Stem cell function and stress response are controlled by protein synthesis. Nature. 2016; 534(7607):335-40. PMC: 5040503. DOI: 10.1038/nature18282. View

11.

Boccaletto P, Machnicka M, Purta E, Piatkowski P, Baginski B, Wirecki T . MODOMICS: a database of RNA modification pathways. 2017 update. Nucleic Acids Res. 2017; 46(D1):D303-D307. PMC: 5753262. DOI: 10.1093/nar/gkx1030. View

12.

Bonnemann C, Belluscio B, Braun S, Morris C, Singh T, Muntoni F . Dystrophin Immunity after Gene Therapy for Duchenne's Muscular Dystrophy. N Engl J Med. 2023; 388(24):2294-2296. DOI: 10.1056/NEJMc2212912. View

13.

Bordeira-Carrico R, Ferreira D, Mateus D, Pinheiro H, Pego A, Santos M . Rescue of wild-type E-cadherin expression from nonsense-mutated cancer cells by a suppressor-tRNA. Eur J Hum Genet. 2014; 22(9):1085-92. PMC: 4135406. DOI: 10.1038/ejhg.2013.292. View

14.

Bray F, Ferlay J, Soerjomataram I, Siegel R, Torre L, Jemal A . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018; 68(6):394-424. DOI: 10.3322/caac.21492. View

15.

Buvoli M, Buvoli A, Leinwand L . Suppression of nonsense mutations in cell culture and mice by multimerized suppressor tRNA genes. Mol Cell Biol. 2000; 20(9):3116-24. PMC: 85606. DOI: 10.1128/MCB.20.9.3116-3124.2000. View

16.

Carollo P, Tutone M, Culletta G, Fiduccia I, Corrao F, Pibiri I . Investigating the Inhibition of FTSJ1, a Tryptophan tRNA-Specific 2'-O-Methyltransferase by NV TRIDs, as a Mechanism of Readthrough in Nonsense Mutated CFTR. Int J Mol Sci. 2023; 24(11). PMC: 10253411. DOI: 10.3390/ijms24119609. View

17.

Chan P, Lowe T . GtRNAdb 2.0: an expanded database of transfer RNA genes identified in complete and draft genomes. Nucleic Acids Res. 2015; 44(D1):D184-9. PMC: 4702915. DOI: 10.1093/nar/gkv1309. View

18.

Chan C, Zhou C, Huang R . Reconstituting bacterial RNA repair and modification in vitro. Science. 2009; 326(5950):247. DOI: 10.1126/science.1179480. View

19.

Chan C, Pham P, Dedon P, Begley T . Lifestyle modifications: coordinating the tRNA epitranscriptome with codon bias to adapt translation during stress responses. Genome Biol. 2018; 19(1):228. PMC: 6307160. DOI: 10.1186/s13059-018-1611-1. View

20.

Chen Q, Yan M, Cao Z, Li X, Zhang Y, Shi J . Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science. 2016; 351(6271):397-400. DOI: 10.1126/science.aad7977. View