ArticleCellular & molecular immunology2019
The methyltransferase PRMT6 attenuates antiviral innate immunity by blocking TBK1-IRF3 signaling.
Article in Cellular & molecular immunology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 67 citations in OpenAlex.
- PRMT6 inhibition or deficiency attenuates diabetic neuropathic pain in male mice and is associated with reduced spinal neuroinflammation, microgliosis, and altered p53-p21 signaling.Journal of neuroinflammation · 2026Article
- PRMT6-mediated EZH2 arginine methylation is critical for breast cancer development.Oncogenesis · 2026Article
- PRMT6 is required for initiating and amplifying macrophage-induced inflammation in heterotopic ossification by increasing CCL2 expression.Bone research · 2026Article
- The Role of Protein Arginine Methylation as a Post-Translational Modification in Cellular Homeostasis and Disease.Biology · 2025Review
- Emerging role of the cGAS-STING pathway in cardiovascular diseases: biologic function, mechanisms and targeted therapy.Molecular medicine (Cambridge, Mass.) · 2025Review
- Lumpy skin disease virus ORF142 protein inhibits type I interferon production by disrupting interactions of TBK1 and IRF3.BMC veterinary research · 2025Article
- Article
- Uncovering cell-type-specific immunomodulatory variants and molecular phenotypes in COVID-19 using structurally resolved protein networks.Cell reports · 2024Article
- Targeting PRMT7-mediated monomethylation of MAVS enhances antiviral innate immune responses and inhibits RNA virus replication.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- PRMT6 Epigenetically Drives Metabolic Switch from Fatty Acid Oxidation toward Glycolysis and Promotes Osteoclast Differentiation During Osteoporosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- HSV-1 reactivation results in post-herpetic neuralgia by upregulating Prmt6 and inhibiting cGAS-STING.Brain : a journal of neurology · 2024Article
- The Role of Protein Methyltransferases in Immunity.Molecules (Basel, Switzerland) · 2024Review
- Asymmetric arginine dimethylation of cytosolic RNA and DNA sensors by PRMT3 attenuates antiviral innate immunity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- PRMT1 mediated methylation of cGAS suppresses anti-tumor immunity.Nature communications · 2023Article
- Avian Metapneumovirus Subgroup C Phosphoprotein Suppresses Type I Interferon Production by Blocking Interferon Regulatory Factor 3 Nuclear Translocation.Microbiology spectrum · 2023Article
- Protein arginine methylation in viral infection and antiviral immunity.International journal of biological sciences · 2023Review
- The emerging roles of protein arginine methyltransferases in antiviral innate immune signaling pathways.Frontiers in microbiology · 2023Review
- TBK1 and IRF3 are potential therapeutic targets in Enterovirus A71-associated diseases.PLoS neglected tropical diseases · 2023Article
- eIF4A3 Promotes RNA Viruses' Replication by Inhibiting Innate Immune Responses.Journal of virology · 2022Article
- Long noncoding RNA IRF1-AS is associated with peste des petits ruminants infection.Veterinary research · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein arginine methyltransferases (PRMTs) play diverse biological roles and are specifically involved in immune cell development and inflammation. However, their role in antiviral innate immunity has not been elucidated. Viral infection triggers the TBK1-IRF3 signaling pathway to stimulate the production of type-I interferon, which mediates antiviral immunity. We performed a functional screen of the nine mammalian PRMTs for regulators of IFN-β expression and found that PRMT6 inhibits the antiviral innate immune response. Viral infection also upregulated PRMT6 protein levels. We generated PRMT6-deficient mice and found that they exhibited enhanced antiviral innate immunity. PRMT6 deficiency promoted the TBK1-IRF3 interaction and subsequently enhanced IRF3 activation and type-I interferon production. Mechanistically, viral infection enhanced the binding of PRMT6 to IRF3 and inhibited the interaction between IRF3 and TBK1; this mechanism was independent of PRMT6 methyltransferase activity. Thus, PRMT6 inhibits antiviral innate immunity by sequestering IRF3, thereby blocking TBK1-IRF3 signaling. Our work demonstrates a methyltransferase-independent role for PRMTs. It also identifies a negative regulator of the antiviral immune response, which may protect the host from the damaging effects of an overactive immune system and/or be exploited by viruses to escape immune detection.
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