Pivotal role of RNA-binding E3 ubiquitin ligase MEX3C in RIG-I-mediated antiviral innate immunity

Kanako Kuniyoshi, Osamu Takeuchi, Surya Pandey, Takashi Satoh, Hidenori Iwasaki, Shizuo Akira*, Taro Kawai

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

90 Scopus citations

Abstract

The RIG-I-like receptors, retinoic acid inducible gene-1 (RIG-I), melanoma differentiation-Associated protein 5, and laboratory of genetics and physiology-2, are cytoplasmic sensors for RNA viruses that mediate the antiviral innate immune responses. We demonstrate that really interesting new gene-finger domain- and K homology domain-containing MEX3C regulates RIG-I function. MEX3C colocalizes with RIG-I in the stress granules of virally infected cells, and its overexpression causes the lysine-63-linked ubiquitination of RIG-I and activates IFN-β promoter. Embryonic fibroblast cells, macrophages, and conventional dendritic cells derived from Mex3cdeficient mice showed defective production of type I IFN after infection with RNA viruses that are recognized by RIG-I. These results demonstrate that MEX3C is an E3 ubiquitin ligase that modifies RIG-I in stress granules and plays a critical role in eliciting antiviral immune responses.

Original languageEnglish (US)
Pages (from-to)5646-5651
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number15
DOIs
StatePublished - Apr 15 2014
Externally publishedYes

Keywords

  • Cytoplasmic puncta
  • Signal transduction

ASJC Scopus subject areas

  • General

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