The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
A Conserved Histidine in the RNA Sensor RIG-I Controls Immune Tolerance to N1-2′O-Methylated Self RNA
Open accessAbstract
The cytosolic helicase retinoic acid-inducible gene-I (RIG-I) initiates immune responses to most RNA viruses by detecting viral 5′-triphosphorylated RNA (pppRNA). Although endogenous mRNA is also 5′-triphosphorylated, backbone modifications and the 5′-ppp-linked methylguanosine (m7G) cap prevent immunorecognition. Here we show that the methylation status of endogenous capped mRNA at the 5′-terminal nucleotide (N1) was crucial to prevent RIG-I activation. Moreover, we identified a single conserved amino acid (H830) in the RIG-I RNA binding pocket as the mediator of steric exclusion of N1-2′O-methylated RNA. H830A alteration (RIG-I(H830A)) restored binding of N1-2′O-methylated pppRNA. Consequently, endogenous mRNA activated the RIG-I(H830A) mutant but not wild-type RIG-I. Similarly, knockdown of the endogenous N1-2′O-methyltransferase led to considerable RIG-I stimulation in the absence of exogenous stimuli. Studies involving yellow-fever-virus-encoded 2′O-methyltransferase and RIG-I(H830A) revealed that viruses exploit this mechanism to escape RIG-I. Our data reveal a new role for cap N1-2′O-methylation in RIG-I tolerance of self-RNA.
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Cites
Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K. J., et al. (2006) · Nature · doi:10.1038/nature04734 · Cited by 3,888
RIG-I-mediated antiviral responses to single-stranded RNA bearing 5’-phosphates
Pichlmair, A., Schulz, O., Tan, C. P., Näslund, T. I., Liljeström, P., Weber, F., & Reis e Sousa, C. (2006) · Science · doi:10.1126/science.1132998 · Cited by 2,210
Distinct RIG-I and MDA5 Signaling by RNA Viruses in Innate Immunity
Loo, Y.-M., Fornek, J., Crochet, N., Bajwa, G., Perwitasari, O., Martinez-Sobrido, L., Akira, S., Gill, M. A., García-Sastre, A., Katze, M. G., et al. (2008) · Journal of Virology · doi:10.1128/jvi.01080-07 · Cited by 1,071
Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5'-diphosphates
Goubau, D., Schlee, M., Deddouche, S., Pruijssers, A. J., Zillinger, T., Goldeck, M., Schuberth, C., Van der Veen, A. G., Fujimura, T., Rehwinkel, J., et al. (2014) · Nature · doi:10.1038/nature13590 · Cited by 557 · cited 1×
“…inhibiting signatures in putative RIG-I ligands remains to be determined, especially in light of the fact that in vitro transcription was used to study the impact of the latter modifications (Goubau et al., 2014; Schlee et al., 2009; Schmidt et al., 2009; see Supplemental Experimental Procedures).”
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Recognition of Endogenous Nucleic Acids by the Innate Immune System
Roers, A., Hiller, B., & Hornung, V. (2016) · Immunity · doi:10.1016/j.immuni.2016.04.002 · Cited by 541
Self-citationRecent advances in mRNA vaccine technology
Pardi, N., Hogan, M. J., & Weissman, D. (2020) · Current Opinion in Immunology · doi:10.1016/j.coi.2020.01.008 · Cited by 512
Devarkar, S. C., Wang, C., Miller, M. T., Ramanathan, A., Jiang, F., Khan, A. G., Patel, S. S., & Marcotrigiano, J. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1515152113 · Cited by 357
mRNA vaccines for COVID-19: what, why and how
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Metadata
- Authors
- Schuberth-Wagner, C., Ludwig, J., Bruder, A. K., Herzner, A.-M., Zillinger, T., Goldeck, M., Schmidt, T., Schmid-Burgk, J. L., Kerber, R., Wolter, S., Stümpel, J.-P., Roth, A., Bartok, E., Drosten, C., Coch, C., Hornung, V., Barchet, W., Kümmerer, B. M., Hartmann, G., & Schlee, M.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2015-07
- Volume
- 43
- Issue
- 1
- Pages
- 41-51
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W1781506009
- Cited by
- 311
- References
- 4
- FWCI
- 9.62
- Type
- journal article
- Language
- en
- Open access
- bronze
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