HDAC6 regulates cellular viral RNA sensing by deacetylation of RIG‐I |
| |
| Authors: | Jae‐Hoon Kim Song Yi Park Tae‐Hwan Kim Woon‐Kyu Lee Duk‐Jae Jang Ji‐Eun Yoon Young‐Il Choi Seihwan Kim JinYeul Ma Chul‐Joong Kim Tso‐Pang Yao Jae U Jung Joo‐Yong Lee Jong‐Soo Lee |
| |
| Affiliation: | 1. College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Korea;2. Graduate School of Analytical Science and Technology (GRAST), Chungnam National University, Daejeon, Korea;3. College of Medicine, Inha University, Incheon, Korea;4. Foot and Mouth Disease Division, Animal Quarantine and Inspection Agency, Anyang, Korea;5. CKD Research Institute, Yongin‐si, Gyeonggi‐do, Korea;6. Korean Medicine (KM) Based Herbal Drug Development Group, Korea Institute of Oriental Medicine, Daejeon, Korea;7. Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA;8. Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA |
| |
| Abstract: | ![]()
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 wild‐type mice. These findings underscore the critical role of HDAC6 in the modulation of the RIG‐I‐mediated antiviral sensing pathway. |
| |
| Keywords: | deacetylation HDAC6 innate immunity RIG‐I virus sensing |
|
|
