Histone demethylase LSD1 promotes RIG-I poly-ubiquitination and anti-viral gene expression.

Under RNA virus infection, retinoic acid-inducible gene I (RIG-I) in host cells recognizes viral RNA and activates the expression of type I IFN. To investigate the roles of protein methyltransferases and demethylases in RIG-I antiviral signaling pathway, we screened all the known related enzymes wit...

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Autores principales:	Qi-Xin Hu, Hui-Yi Wang, Lu Jiang, Chen-Yu Wang, Lin-Gao Ju, Yuan Zhu, Bo Zhong, Min Wu, Zhen Wang, Lian-Yun Li
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e15c412e544344ef9f6012a841f1f5db
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spelling	oai:doaj.org-article:e15c412e544344ef9f6012a841f1f5db2021-12-02T20:00:10ZHistone demethylase LSD1 promotes RIG-I poly-ubiquitination and anti-viral gene expression.1553-73661553-737410.1371/journal.ppat.1009918https://doaj.org/article/e15c412e544344ef9f6012a841f1f5db2021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009918https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Under RNA virus infection, retinoic acid-inducible gene I (RIG-I) in host cells recognizes viral RNA and activates the expression of type I IFN. To investigate the roles of protein methyltransferases and demethylases in RIG-I antiviral signaling pathway, we screened all the known related enzymes with a siRNA library and identified LSD1 as a positive regulator for RIG-I signaling. Exogenous expression of LSD1 enhances RIG-I signaling activated by virus stimulation, whereas its deficiency restricts it. LSD1 interacts with RIG-I, promotes its K63-linked polyubiquitination and interaction with VISA/MAVS. Interestingly, LSD1 exerts its function in antiviral response not dependent on its demethylase activity but through enhancing the interaction between RIG-I with E3 ligases, especially TRIM25. Furthermore, we provide in vivo evidence that LSD1 increases antiviral gene expression and inhibits viral replication. Taken together, our findings demonstrate that LSD1 is a positive regulator of signaling pathway triggered by RNA-virus through mediating RIG-I polyubiquitination.Qi-Xin HuHui-Yi WangLu JiangChen-Yu WangLin-Gao JuYuan ZhuBo ZhongMin WuZhen WangLian-Yun LiPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 9, p e1009918 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Qi-Xin Hu Hui-Yi Wang Lu Jiang Chen-Yu Wang Lin-Gao Ju Yuan Zhu Bo Zhong Min Wu Zhen Wang Lian-Yun Li Histone demethylase LSD1 promotes RIG-I poly-ubiquitination and anti-viral gene expression.
description	Under RNA virus infection, retinoic acid-inducible gene I (RIG-I) in host cells recognizes viral RNA and activates the expression of type I IFN. To investigate the roles of protein methyltransferases and demethylases in RIG-I antiviral signaling pathway, we screened all the known related enzymes with a siRNA library and identified LSD1 as a positive regulator for RIG-I signaling. Exogenous expression of LSD1 enhances RIG-I signaling activated by virus stimulation, whereas its deficiency restricts it. LSD1 interacts with RIG-I, promotes its K63-linked polyubiquitination and interaction with VISA/MAVS. Interestingly, LSD1 exerts its function in antiviral response not dependent on its demethylase activity but through enhancing the interaction between RIG-I with E3 ligases, especially TRIM25. Furthermore, we provide in vivo evidence that LSD1 increases antiviral gene expression and inhibits viral replication. Taken together, our findings demonstrate that LSD1 is a positive regulator of signaling pathway triggered by RNA-virus through mediating RIG-I polyubiquitination.
format	article
author	Qi-Xin Hu Hui-Yi Wang Lu Jiang Chen-Yu Wang Lin-Gao Ju Yuan Zhu Bo Zhong Min Wu Zhen Wang Lian-Yun Li
author_facet	Qi-Xin Hu Hui-Yi Wang Lu Jiang Chen-Yu Wang Lin-Gao Ju Yuan Zhu Bo Zhong Min Wu Zhen Wang Lian-Yun Li
author_sort	Qi-Xin Hu
title	Histone demethylase LSD1 promotes RIG-I poly-ubiquitination and anti-viral gene expression.
title_short	Histone demethylase LSD1 promotes RIG-I poly-ubiquitination and anti-viral gene expression.
title_full	Histone demethylase LSD1 promotes RIG-I poly-ubiquitination and anti-viral gene expression.
title_fullStr	Histone demethylase LSD1 promotes RIG-I poly-ubiquitination and anti-viral gene expression.
title_full_unstemmed	Histone demethylase LSD1 promotes RIG-I poly-ubiquitination and anti-viral gene expression.
title_sort	histone demethylase lsd1 promotes rig-i poly-ubiquitination and anti-viral gene expression.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/e15c412e544344ef9f6012a841f1f5db
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Histone demethylase LSD1 promotes RIG-I poly-ubiquitination and anti-viral gene expression.

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