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:10.1371/journal.ppat.1008387

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. eCollection 2020 Mar.

Authors

Bo Yang^{1

2}, Yue Liu¹, Yuhan Cui¹, Di Song¹, Ge Zhang¹, Shujun Ma¹, Yanzi Liu³, Mengmeng Chen¹, Fan Chen¹, Hui Wang², 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.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (31600697, U1704183, 31970847)31600697 (J.W.), U1704183 (B.Y.) and 31970847 (J.W.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.