Ribose 2'-O-methylation provides a molecular signature for the distinction of self and non-self mRNA dependent on the RNA sensor Mda5
Open accessAbstract
The 5' cap structures of higher eukaryote mRNAs have ribose 2'-O-methylation. Likewise, many viruses that replicate in the cytoplasm of eukaryotes have evolved 2'-O-methyltransferases to autonomously modify their mRNAs. However, a defined biological role for 2'-O-methylation of mRNA remains elusive. Here we show that 2'-O-methylation of viral mRNA was critically involved in subverting the induction of type I interferon. We demonstrate that human and mouse coronavirus mutants lacking 2'-O-methyltransferase activity induced higher expression of type I interferon and were highly sensitive to type I interferon. Notably, the induction of type I interferon by viruses deficient in 2'-O-methyltransferase was dependent on the cytoplasmic RNA sensor Mda5. This link between Mda5-mediated sensing of viral RNA and 2'-O-methylation of mRNA suggests that RNA modifications such as 2'-O-methylation provide a molecular signature for the discrimination of self and non-self mRNA.
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- Authors
- Züst, R., Cervantes-Barragan, L., Habjan, M., Maier, R., Neuman, B. W., Ziebuhr, J., Szretter, K. J., Baker, S. C., Barchet, W., Diamond, M. S., Siddell, S. G., Ludewig, B., & Thiel, V.
- Affiliations
- Agency for Science, Technology and Research (SG)
- Kantonsspital St. Gallen (CH)
- University of Reading (GB)
- Queen's University Belfast (GB)
- Washington University in St. Louis (US)
- Loyola University Medical Center (US)
- University of Bonn (DE)
- University of Bristol (GB)
- University of Zurich (CH)
- Corresponding author
- Thiel, Volker
- ORCID
- Venue
- Nature Immunology
- Published
- 2011-01-09
- Volume
- 12
- Issue
- 2
- Pages
- 137-143
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- PMC
- PMC3182538
- OpenAlex
- W2099866950
- Cited by
- 811
- References
- 49
- Citations by year
- 2026: 27 · 2025: 39 · 2024: 46 · 2023: 56 · 2022: 72 · 2021: 95 · 2020: 109 · 2019: 42 · 2018: 43 · 2017: 38 · 2016: 42 · 2015: 49 · 2014: 46 · 2013: 41 · 2012: 45
- FWCI
- 21.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Nature Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- CentAUR (University of Reading) (acceptedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Funders
- National Science Foundation
- Novartis Foundation
- Wellcome Trust
- Imperial College London
- European Commission
- Deutsche Forschungsgemeinschaft
- Universität Heidelberg
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Austrian Science Fund (J3044)
- National Institutes of Health
- Medical Research Council
- Biotechnology and Biological Sciences Research Council (BB/G012067/1)
- National Institute of Allergy and Infectious Diseases (P01AI060915, U54AI081680, AI060915, AI085089, R01AI085089)
- Institute of Genetics
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- MDA5, type I interferon induction, interferon sensitivity, viral RNA sensing, coronavirus, RNA modification
- MeSH terms
- Interferon-Induced Helicase, IFIH1, Animals, Cell Line, Humans, Immunity, Innate, Interferon Type I, Methylation, Methyltransferases, Mice, Inbred C57BL, Ribose, RNA, Viral, Viral Proteins, Virulence, Virus Replication, Coronavirus, Mice, Knockout, Coronavirus Infections, Receptors, Pattern Recognition, Mice, DEAD-box RNA Helicases, Receptor, Interferon alpha-beta
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