Open AccessRNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation
Author(s) -
Bo Yang,
Yue Liu,
Yuhan Cui,
Di Song,
Ge Zhang,
Shujun Ma,
Yanzi Liu,
Mengmeng Chen,
Fan Chen,
Hui Wang,
Jie Wang
Publication year - 2020
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1008387
Subject(s) - innate immune system , microbiology and biotechnology , biology , proteasome , dna virus , ubiquitin , irf3 , gene knockdown , cytosol , signal transducing adaptor protein , immune system , dna , signal transduction , immunology , apoptosis , gene , biochemistry , genome , enzyme
Mediator of IRF3 activation (MITA, also named as STING/ERIS/MPYS/TMEM173), is essential to DNA virus- or cytosolic DNA-triggered innate immune responses. In this study, we demonstrated the negative regulatory role of RING-finger protein (RNF) 90 in innate immune responses targeting MITA. RNF90 promoted K48-linked ubiquitination of MITA and its proteasome-dependent degradation. Overexpression of RNF90 inhibited HSV-1- or cytosolic DNA-induced immune responses whereas RNF90 knockdown had the opposite effects. Moreover, RNF90-deficient bone marrow-derived dendritic cells (BMDCs), bone marrow-derived macrophages (BMMs) and mouse embryonic fibroblasts (MEFs) exhibited increased DNA virus- or cytosolic DNA-triggered signaling and RNF90 deficiency protected mice from DNA virus infection. Taken together, our findings suggested a novel function of RNF90 in innate immunity.