PLoS Pathogens (Mar 2020)

RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation.

  • Bo Yang,
  • Yue Liu,
  • Yuhan Cui,
  • Di Song,
  • Ge Zhang,
  • Shujun Ma,
  • Yanzi Liu,
  • Mengmeng Chen,
  • Fan Chen,
  • Hui Wang,
  • Jie Wang

DOI
https://doi.org/10.1371/journal.ppat.1008387
Journal volume & issue
Vol. 16, no. 3
p. e1008387

Abstract

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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.