Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Highlight
  • Published:

The m1A modification of tRNAs: a translational accelerator of T-cell activation

Cellular & Molecular Immunology volume 19, pages 1328–1329 (2022)Cite this article

Subjects

Access through your institution
Buy or subscribe

Upon antigen stimulation, naïve T cells exit the quiescent state and undergo rapid clonal expansion and differentiation [1]. This cell fate transition requires accelerated protein synthesis, which is regulated at both the transcriptional and translational levels [2, 3]. Compared with well-documented transcriptional regulatory mechanisms, the translational regulation of T-cell activation has not been fully elucidated. A recent study by Liu et al. published in Nature Immunology suggested that the tRNA m1A58 modification is an important regulatory mechanism of T-cell activation [4].

During translation, tRNAs play important roles in decoding mRNA. In addition to their abundance, the modification and aminoacylation (charge) status of tRNAs is essential to ensure translation efficiency and fidelity [5, 6]. To date, more than 170 RNA modifications have been documented, and most of them have been identified in tRNAs [7]. On average, one tRNA molecule harbors 13 modifications that affect protein synthesis through several mechanisms, including tRNA stability, codon recognition, and aminoacylation capability [5]. Among these modifications, N1-methyladenosine (m1A), which is typically found at position 58 in cytoplasmic tRNA and is catalyzed by the TRMT6/61 A complex to enhance translation initiation and elongation, is among the most conserved [8]. A recent study reported that tRNA m1A58 methylation was required for liver tumorigenesis, but its physiological roles in T-cell activation remained to be investigated [9].

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1

References

  1. Saravia J, Chapman NM, Chi H. Helper T cell differentiation. Cell Mol Immunol. 2019;16:634–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Tan H, Yang K, Li Y, Shaw TI, Wang Y, Blanco DB, et al. Integrative proteomics and phosphoproteomics profiling reveals dynamic signaling networks and bioenergetics pathways underlying T cell activation. Immunity 2017;46:488–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Li HB, Tong J, Zhu S, Batista PJ, Duffy EE, Zhao J, et al. m(6)A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways. Nature 2017;548:338–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Liu Y, Zhou J, Li X, Zhang X, Shi J, Wang X, et al. tRNA-m1A modification promotes T cell expansion via efficient MYC protein synthesis. Nat Immunol. 2022;23:1433–44.

    Article  CAS  PubMed  Google Scholar 

  5. Pan T. Modifications and functional genomics of human transfer RNA. Cell Res. 2018;28:395–404.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Suzuki T. The expanding world of tRNA modifications and their disease relevance. Nat Rev Mol Cell Bio. 2021;22:375–92.

    Article  CAS  Google Scholar 

  7. Boccaletto P, Stefaniak F, Ray A, Cappannini A, Mukherjee S, Purta E, et al. MODOMICS: a database of RNA modification pathways. 2021 update. Nucleic Acids Res. 2022;50:D231–D5.

    Article  CAS  PubMed  Google Scholar 

  8. Liu F, Clark W, Luo G, Wang X, Fu Y, Wei J, et al. ALKBH1-mediated tRNA demethylation regulates translation. Cell 2016;167:1897.

    Article  CAS  PubMed  Google Scholar 

  9. Wang Y, Wang J, Li X, Xiong X, Wang J, Zhou Z, et al. N(1)-methyladenosine methylation in tRNA drives liver tumourigenesis by regulating cholesterol metabolism. Nat Commun. 2021;12:6314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhong Y, Walker SK, Pritykin Y, Leslie CS, Rudensky AY, Van der Veeken J. Hierarchical regulation of the resting and activated T cell epigenome by major transcription factor families. Nat Immunol. 2022;23:122.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We appreciate helpful discussions with Dr. Qin Tian and Dr. Yifei Wang.

Author information

Authors and Affiliations

  1. Institute of Immunology, Third Military Medical University, Chongqing, 400038, China

    Cheng Chen & Lilin Ye

Authors
  1. Cheng Chen
    View author publications

    Search author on:PubMed Google Scholar

  2. Lilin Ye
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Lilin Ye.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, C., Ye, L. The m1A modification of tRNAs: a translational accelerator of T-cell activation. Cell Mol Immunol 19, 1328–1329 (2022). https://doi.org/10.1038/s41423-022-00942-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41423-022-00942-6

This article is cited by

Search

Advanced search

Quick links