RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation

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 promo...

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Autores principales: Yang, Bo, Liu, Yue, Cui, Yuhan, Song, Di, Zhang, Ge, Ma, Shujun, Liu, Yanzi, Chen, Mengmeng, Chen, Fan, Wang, Hui, Wang, Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069649/
https://www.ncbi.nlm.nih.gov/pubmed/32126128
http://dx.doi.org/10.1371/journal.ppat.1008387
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author Yang, Bo
Liu, Yue
Cui, Yuhan
Song, Di
Zhang, Ge
Ma, Shujun
Liu, Yanzi
Chen, Mengmeng
Chen, Fan
Wang, Hui
Wang, Jie
author_facet Yang, Bo
Liu, Yue
Cui, Yuhan
Song, Di
Zhang, Ge
Ma, Shujun
Liu, Yanzi
Chen, Mengmeng
Chen, Fan
Wang, Hui
Wang, Jie
author_sort Yang, Bo
collection PubMed
description 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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spelling pubmed-70696492020-03-23 RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation Yang, Bo Liu, Yue Cui, Yuhan Song, Di Zhang, Ge Ma, Shujun Liu, Yanzi Chen, Mengmeng Chen, Fan Wang, Hui Wang, Jie PLoS Pathog Research Article 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. Public Library of Science 2020-03-03 /pmc/articles/PMC7069649/ /pubmed/32126128 http://dx.doi.org/10.1371/journal.ppat.1008387 Text en © 2020 Yang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Yang, Bo
Liu, Yue
Cui, Yuhan
Song, Di
Zhang, Ge
Ma, Shujun
Liu, Yanzi
Chen, Mengmeng
Chen, Fan
Wang, Hui
Wang, Jie
RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation
title RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation
title_full RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation
title_fullStr RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation
title_full_unstemmed RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation
title_short RNF90 negatively regulates cellular antiviral responses by targeting MITA for degradation
title_sort rnf90 negatively regulates cellular antiviral responses by targeting mita for degradation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7069649/
https://www.ncbi.nlm.nih.gov/pubmed/32126128
http://dx.doi.org/10.1371/journal.ppat.1008387
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