RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation

  • PLoS Pathog. 2020 Mar 3;16(3):e1008387. doi: 10.1371/journal.ppat.1008387.
Bo Yang  1  2 ,  Yue Liu  1 ,  Yuhan Cui  1 ,  Di Song  1 ,  Ge Zhang  1 ,  Shujun Ma  1 ,  Yanzi Liu  3 ,  Mengmeng Chen  1 ,  Fan Chen  1 ,  Hui Wang  2 ,  Jie Wang  1  2
Affiliations
  • 1. Henan Key Laboratory of immunology and targeted drug, Xinxiang Medical University, Xinxiang, Henan Province, China.
  • 2. Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, Henan Province, China.
  • 3. Department of Laboratory Medicine, the Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan Province, China.
PMID: 32126128 DOI: 10.1371/journal.ppat.1008387
Abstract

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.