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.

N6-adenosine methylation (m6A) is involved in the life and death decisions of T cells

Cellular & Molecular Immunology (2022)Cite this article

Subjects

N6-adenosine methylation (m6A) is the most abundant modification observed in mRNA transcripts. It is a dynamic modification that is performed by members of the so-called writer complex (including Wtap, Virma and Mettl3) and that can be removed by so-called eraser proteins [1]. In addition, m6A is recognized by reader proteins (including Ythdf2) that can exert a response. Readers and m6A can modify virtually all mRNA processes, including RNA splicing, secondary structures, nuclear export and transcript stability [1]. The functional relevance of m6A-mediated regulation in specific cell types and treatment conditions remains only partly understood. In T cells, earlier studies have demonstrated a relevant role for m6A in T effector (Teff), T follicular helper (TFH) and T regulatory (Treg) cells through manipulation of m6A pathway genes in mice [2,3,4,5,6]. In these studies, disruption of m6A resulted in dysregulation of gene expression patterns and caused colitis and systemic autoinflammatory disease. In a recent study by Ito-Kureha et al., the authors set out to further understand how m6A signaling affects T-cell functions by manipulating Wtap in select T cells with a murine knockout model [7]. They found that m6A signaling controls many aspects of T-cell immunobiology: activation, proliferation, life, and death.

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

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

References

  1. Zaccara S, Ries RJ, Jaffrey SR. Reading, writing and erasing mRNA methylation. Nat Rev Mol Cell Biol. 2019;20:608–24.

    Article  PubMed  CAS  Google Scholar 

  2. Li HB, Tong J, Zhu S, Batista PJ, Duffy EE, Zhao J, et al. M6A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways. Nature. 2017;548:338–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Yao Y, Yang Y, Guo W, Xu L, You M, Zhang YC, et al. METTL3-dependent m6A modification programs T follicular helper cell differentiation. Nat Commun. 2021;12:1–16.

    Article  Google Scholar 

  4. Tong J, Cao G, Zhang T, Sefik E, Vesely MCA, Broughton JP, et al. M6 A mRNA methylation sustains Treg suppressive functions. Cell Res. 2018;28:253–6.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lu TX, Zheng Z, Zhang L, Sun HL, Bissonnette M, Huang H, et al. A new model of spontaneous colitis in mice induced by deletion of an RNA m6A methyltransferase component METTL14 in T cells. Cmgh. 2020;10:747–61.

    PubMed  PubMed Central  Google Scholar 

  6. Sprent J, Surh CD. Writer’s block: Preventing m 6 A mRNA methylation promotes T cell naivety. Immunol Cell Biol. 2017;95:855–6.

    Article  PubMed  CAS  Google Scholar 

  7. Ito-Kureha T, Leoni C, Borland K, Cantini G, Bataclan M, Metzger RN, et al. The function of Wtap in N 6-adenosine methylation of mRNAs controls T cell receptor signaling and survival of T cells. Nat Immunol. 2022;23:1208–21.

    Article  PubMed  CAS  Google Scholar 

  8. Zaccara S, Jaffrey SR. A unified model for the function of YTHDF proteins in regulating m6A-Modified mRNA. Cell. 2020;181:1582–1595.e18.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Tegowski M, Flamand MN, Meyer KD. scDART-seq reveals distinct m6A signatures and mRNA methylation heterogeneity in single cells. Mol Cell. 2022;82:868–878.e10.

    Article  PubMed  CAS  Google Scholar 

  10. Workman RE, Tang AD, Tang PS, Jain M, Tyson JR, Razaghi R, et al. Nanopore native RNA sequencing of a human poly(A) transcriptome. Nat Methods. 2019;16:1297–305.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

Download references

Author information

Author notes

  1. These authors contributed equally: J.J.A. Calis, J. van Loosdregt.

Authors and Affiliations

  1. Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands

    J. J. A. Calis & J. van Loosdregt

  2. Pediatric Immunology & Rheumatology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands

    J. J. A. Calis

Authors
  1. J. J. A. Calis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. van Loosdregt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. van Loosdregt.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Calis, J.J.A., van Loosdregt, J. N6-adenosine methylation (m6A) is involved in the life and death decisions of T cells. Cell Mol Immunol (2022). https://doi.org/10.1038/s41423-022-00958-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41423-022-00958-y

Search

Advanced search

Quick links