2. Academic Validation
  3. RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation

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

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.

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