Structural basis for m7G recognition and 2′-O-methyl discrimination in capped RNAs by the innate immune receptor RIG-I
Open accessAbstract
Significance: The cytosolic innate immune receptor Retinoic Acid Inducible Gene-I (RIG-I) is the principal detector of pathogenic RNAs carrying a 5′-triphosphate (5′ppp). Self RNAs like mRNAs evade recognition by RIG-I due to posttranscriptional modifications like 5′-end capping with 7-methyl guanosine (m7G) and 2′-O-methylation of 5′-end nucleotides. Viruses have also evolved mechanisms to mimic these modifications, which in part is believed to aid in immune evasion. Currently, it is unclear how these modifications modulate RIG-I recognition. This paper provides structural and mechanistic insights into the roles of the m7G cap and 2′-O-methylation in RIG-I evasion. We show that RIG-I accommodates the m7G base while maintaining the 5′ppp contacts and can recognize Cap-0 RNAs but not Cap-1.
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The 5′-cap structure is a key factor in the host's ability to differentiate between self and non-self mRNA molecules.
“The 5′-cap structure is a key factor in the host's ability to differentiate between self and non-self mRNA molecules (Devarkar et al. 2016).”
From Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency (2022) · cites this paper as Devarkar et al. 2016
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- Authors
- Devarkar, S. C., Wang, C., Miller, M. T., Ramanathan, A., Jiang, F., Khan, A. G., Patel, S. S., & Marcotrigiano, J.
- Affiliations
- Rutgers, The State University of New Jersey (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-01-05
- Volume
- 113
- Issue
- 3
- Pages
- 596-601
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4725518
- OpenAlex
- W2228117528
- Cited by
- 357
- References
- 0
- Citations by year
- 2026: 29 · 2025: 30 · 2024: 49 · 2023: 45 · 2022: 38 · 2021: 41 · 2020: 32 · 2019: 26 · 2018: 30 · 2017: 21 · 2016: 16
- FWCI
- 15.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (GM111959, R01GM111959, P41GM103485, R35GM118086)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- RIG-I, 7-methylguanosine cap, 2'-O-methylation, RNA capping, 5'-triphosphate RNA, innate immune recognition, double-stranded RNA, ATPase activity, type I interferon signaling, immune evasion, viral RNA recognition, crystal structure
- MeSH terms
- Adenosine Triphosphate, Carrier Proteins, Guanosine, Humans, Hydrolysis, Immunity, Innate, Methylation, Nucleic Acid Conformation, RNA, RNA Caps, RNA, Double-Stranded, Signal Transduction, Protein Structure, Tertiary, Crystallography, X-Ray, RNA Helicases, Amino Acid Motifs, HEK293 Cells
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