HDAC6 regulates cellular viral RNA sensing by deacetylation of RIG-I.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Choi, SJ; Lee, H-C; Kim, J-H; Park, SY; Kim, T-H; Lee, W-K; Jang, D-J; Yoon, J-E; Choi, Y-I; Kim, S; Ma, J; Kim, C-J; Yao, T-P; Jung, JU; Lee, J-Y; Lee, J-S

Published Date

  • February 15, 2016

Published In

Volume / Issue

  • 35 / 4

Start / End Page

  • 429 - 442

PubMed ID

  • 26746851

Pubmed Central ID

  • PMC4755110

Electronic International Standard Serial Number (EISSN)

  • 1460-2075

Digital Object Identifier (DOI)

  • 10.15252/embj.201592586


  • eng

Conference Location

  • England