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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.

SUBMITTER: Yang B

PROVIDER: S-EPMC7069649 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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

Yang Bo B Liu Yue Y Cui Yuhan Y Song Di D Zhang Ge G Ma Shujun S Liu Yanzi Y Chen Mengmeng M Chen Fan F Wang Hui H Wang Jie J

PLoS pathogens 20200303 3

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 oppos ...[more]

PMID: 32126128

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