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Cited by 74interferon and immune responsesRNA and protein synthesis mechanismsImmune Response and Inflammation

Infection-specific phosphorylation of glutamyl-prolyl tRNA synthetase induces antiviral immunity

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Lee, Eun-Young, Lee, Hyun-Cheol, Kim, Hyun-Kwan, Jang, Song Yee, Park, Seong-Jun, Kim, Yong-Hoon, Kim, Jong Hwan, Hwang, Jungwon +12 more·2016·Nature Immunology
DOI 10.1038/ni.3542PMC PMC5173487
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Abstract

The mammalian cytoplasmic multi-tRNA synthetase complex (MSC) is a depot system that regulates non-translational cellular functions. Here we found that the MSC component glutamyl-prolyl-tRNA synthetase (EPRS) switched its function following viral infection and exhibited potent antiviral activity. Infection-specific phosphorylation of EPRS at Ser990 induced its dissociation from the MSC, after which it was guided to the antiviral signaling pathway, where it interacted with PCBP2, a negative regulator of mitochondrial antiviral signaling protein (MAVS) that is critical for antiviral immunity. This interaction blocked PCBP2-mediated ubiquitination of MAVS and ultimately suppressed viral replication. EPRS-haploid (Eprs+/-) mice showed enhanced viremia and inflammation and delayed viral clearance. This stimulus-inducible activation of MAVS by EPRS suggests an unexpected role for the MSC as a regulator of immune responses to viral infection.

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  • Many ARSs respond to stimuli, including viral infection, immune activation, and toxins.

    “Many ARSs respond to stimuli, including viral infection, immune activation, and toxins (18, 23, 129).”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [23]

    The Results section reports changes in ARS-related gene expression after viral infection, and the introductory text describes EPRS responding to interferon-γ stimulation. The paper also discusses several MSC components responding to stress, but the passages do not identify toxins as a stimulus for ARSs. No page numbers were provided in our copy. (LLM, conf=0.85)

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  • EPRS inhibits the replication of RNA viruses, including vesicular stomatitis virus and influenza A virus, by promoting the innate immune response via up-regulation of the mitochondrial antiviral signaling protein.

    “EPRS has been shown to inhibit the replication of RNA viruses, including vesicular stomatitis virus and influenza A virus by promoting the innate immune response via up-regulation of the mitochondrial antiviral signaling protein (23).”

    From Role of host tRNAs and aminoacyl-tRNA synthetases in retroviral replication (2019) · cites this paper as [23]

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Authors
Lee, E.-Y., Lee, H.-C., Kim, H.-K., Jang, S. Y., Park, S.-J., Kim, Y.-H., Kim, J. H., Hwang, J., Kim, J.-H., Kim, T.-H., Arif, A., Kim, S.-Y., Choi, Y.-K., Lee, C., Lee, C.-H., Jung, J. U., Fox, P. L., Kim, S., Lee, J.-S., & Kim, M. H.
Affiliations
  • Korea Research Institute of Bioscience and Biotechnology (KR)
  • Chungnam National University (KR)
  • Korea Institute of Science and Technology (KR)
  • Cleveland Clinic (US)
  • Chungbuk National University (KR)
  • University of Southern California (US)
Corresponding author
  • Kim, Tae-Hwan
  • Lee, Jong-Soo
ORCID
Venue
Nature Immunology
Publisher
Springer Science and Business Media LLC
Published
2016-09-05
Volume
17
Issue
11
Pages
1252-1262
ISSN
  • 1529-2908 (ISSN-L)
  • 1529-2916
DOI
10.1038/ni.3542
PMC
PMC5173487
OpenAlex
W2508327349
Cited by
74
References
3
Citations by year
2026: 7 · 2025: 3 · 2024: 7 · 2023: 10 · 2022: 7 · 2021: 4 · 2020: 13 · 2019: 9 · 2018: 6 · 2017: 6 · 2016: 2
FWCI
4.65
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • KRIBB Repository (submittedVersion)
Funders
  • National Heart, Lung, and Blood Institute (P01HL029582)
  • National Cancer Institute (R01CA082057)
  • National Institute of Allergy and Infectious Diseases (R01AI116585)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords
glutamyl-prolyl-tRNA synthetase, tRNA synthetase, MAVS, PCBP2, ubiquitination, antiviral immunity, viral infection, phosphorylation, viral replication
MeSH terms
Amino Acyl-tRNA Synthetases, Animals, Antiviral Agents, Disease Models, Animal, Immunity, Innate, Peptides, Phosphorylation, Protein Binding, RNA Virus Infections, RNA Viruses, Virus Diseases, Virus Replication, Signal Transduction, RNA-Binding Proteins, Mice, Knockout, Mice, Ubiquitination, Host-Pathogen Interactions, Disease Resistance

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