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

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.

• Authors: Bo Yang, Yue Liu, Yuhan Cui, Di Song, Ge Zhang, Shujun Ma, Yanzi Liu, Mengmeng Chen, Fan Chen, Hui Wang, Jie Wang
• Journal: PLoS pathogens (PLoS Pathog) Vol. 16 Issue 3 Pg. e1008387 (03 2020) ISSN: 1553-7374 [Electronic] United States
• PMID: 32126128 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• Sting1 protein, mouse
• Tripartite Motif Proteins
• Trim7 protein, mouse
• Ubiquitin-Protein Ligases

Topics

• Animals
• Bone Marrow Cells (immunology, virology)
• Dendritic Cells (immunology, virology)
• Fibroblasts (immunology, virology)
• Herpesvirus 1, Human (genetics, immunology)
• Immunity, Innate
• Macrophages (immunology, virology)
• Membrane Proteins (genetics, immunology)
• Mice
• Mice, Knockout
• Proteolysis
• Tripartite Motif Proteins (genetics, immunology)
• Ubiquitin-Protein Ligases (genetics, immunology)
• Ubiquitination (genetics, immunology)