Pivotal role of RNA-binding E3 ubiquitin ligase MEX3C in RIG-I-mediated antiviral innate immunity.
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 Mex3c-deficient 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.
Laboratory of Host Defense, World Premier International Immunology Frontier Research Center, and Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Kanako
K
Kuniyoshi
Osamu
O
Takeuchi
Surya
S
Pandey
Takashi
T
Satoh
Hidenori
H
Iwasaki
Shizuo
S
Akira
Taro
T
Kawai
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D015151:Immunoblotting; D047468:Immunoprecipitation; D008156:Luciferases; D051379:Mice; D018345:Mice, Knockout; D016297:Mutagenesis, Site-Directed; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018168:Receptors, Retinoic Acid / Q000276:immunology* / Q000378:metabolism; D054875:Ubiquitination; D014777:Virus Diseases / Q000276:immunology*
D016207:Cytokines; D017931:DNA Primers; C515359:MEX3C protein, human; C437968:PLAAT4 protein, human; D016601:RNA-Binding Proteins; D018168:Receptors, Retinoic Acid; D008156:Luciferases
cytoplasmic puncta; signal transduction