Journal
EMBO JOURNAL
Volume 35, Issue 4, Pages 429-442Publisher
WILEY-BLACKWELL
DOI: 10.15252/embj.201592586
Keywords
deacetylation; HDAC6; innate immunity; RIG-I; virus sensing
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Funding
- Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea [112013032SB010]
- Small and Medium Business Administration [S2130867, S2165234]
- Korean Institute of Oriental Medicine by the Ministry of Education, Science and Technology (MEST) [K12050]
- Korea Healthcare Technology R&D Project - Ministry of Health [A103001]
- National Research Foundation of Korea [2015020957, 2013R1A1A2008576, 2012M3A9C6050087]
- Institute of Planning & Evaluation for Technology in Food, Agriculture, Forestry & Fisheries (iPET), Republic of Korea [112013032SB010] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2012M3A9C6050087, 2013R1A1A2008576] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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RIG-I is a key cytosolic sensor that detects RNA viruses through its C-terminal region and activates the production of antiviral interferons (IFNs) and proinflammatory cytokines. While posttranslational modification has been demonstrated to regulate RIG-I signaling activity, its significance for the sensing of viral RNAs remains unclear. Here, we first show that the RIG-I C-terminal region undergoes deacetylation to regulate its viral RNA-sensing activity and that the HDAC6-mediated deacetylation of RIG-I is critical for viral RNA detection. HDAC6 transiently bound to RIG-I and removed the lysine 909 acetylation in the presence of viral RNAs, promoting RIG-I sensing of viral RNAs. Depletion of HDAC6 expression led to impaired antiviral responses against RNA viruses, but not against DNA viruses. Consequently, HDAC6 knockout mice were highly susceptible to RNA virus infections compared to wildtype mice. These findings underscore the critical role of HDAC6 in the modulation of the RIG-I-mediated antiviral sensing pathway.
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