IRF3-binding lncRNA-ISIR strengthens interferon production in viral infection and autoinflammation

Summary: Interferon regulatory factor 3 (IRF3) is an essential transductor for initiation of many immune responses. Here, we show that lncRNA-ISIR directly binds IRF3 to promote its phosphorylation, dimerization, and nuclear translocation, along with enhanced target gene productions. In vivo lncRNA-...

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Autores principales:	Junfang Xu, Pin Wang, Zemeng Li, Zhiqing Li, Dan Han, Mingyue Wen, Qihang Zhao, Lianfeng Zhang, Yuanwu Ma, Wei Liu, Minghong Jiang, Xuan Zhang, Xuetao Cao
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	innate immunology long noncoding RNA type I interferon infection autoimmunity Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ac0dbf9e59fb4eb680027ce458b31f15
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spelling	oai:doaj.org-article:ac0dbf9e59fb4eb680027ce458b31f152021-11-04T04:29:15ZIRF3-binding lncRNA-ISIR strengthens interferon production in viral infection and autoinflammation2211-124710.1016/j.celrep.2021.109926https://doaj.org/article/ac0dbf9e59fb4eb680027ce458b31f152021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721013991https://doaj.org/toc/2211-1247Summary: Interferon regulatory factor 3 (IRF3) is an essential transductor for initiation of many immune responses. Here, we show that lncRNA-ISIR directly binds IRF3 to promote its phosphorylation, dimerization, and nuclear translocation, along with enhanced target gene productions. In vivo lncRNA-ISIR deficiency results in reduced IFN production, uncontrolled viral replication, and increased mortality. The human homolog, AK131315, also binds IRF3 and promotes its activation. More important, AK131315 expression is positively correlated with type I interferon (IFN-I) level and severity in patients with lupus. Mechanistically, in resting cells, IRF3 is bound to suppressor protein Flightless-1 (Fli-1), which keeps its inactive state. Upon infection, IFN-I-induced lncRNA-ISIR binds IRF3 at DNA-binding domain in cytoplasm and removes Fli-1’s association from IRF3, consequently facilitating IRF3 activation. Our results demonstrate that IFN-I-inducible lncRNA-ISIR feedback strengthens IRF3 activation by removing suppressive Fli-1 in immune responses, revealing a method of lncRNA-mediated modulation of transcription factor (TF) activation.Junfang XuPin WangZemeng LiZhiqing LiDan HanMingyue WenQihang ZhaoLianfeng ZhangYuanwu MaWei LiuMinghong JiangXuan ZhangXuetao CaoElsevierarticleinnate immunologylong noncoding RNAtype I interferoninfectionautoimmunityBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 5, Pp 109926- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	innate immunology long noncoding RNA type I interferon infection autoimmunity Biology (General) QH301-705.5
spellingShingle	innate immunology long noncoding RNA type I interferon infection autoimmunity Biology (General) QH301-705.5 Junfang Xu Pin Wang Zemeng Li Zhiqing Li Dan Han Mingyue Wen Qihang Zhao Lianfeng Zhang Yuanwu Ma Wei Liu Minghong Jiang Xuan Zhang Xuetao Cao IRF3-binding lncRNA-ISIR strengthens interferon production in viral infection and autoinflammation
description	Summary: Interferon regulatory factor 3 (IRF3) is an essential transductor for initiation of many immune responses. Here, we show that lncRNA-ISIR directly binds IRF3 to promote its phosphorylation, dimerization, and nuclear translocation, along with enhanced target gene productions. In vivo lncRNA-ISIR deficiency results in reduced IFN production, uncontrolled viral replication, and increased mortality. The human homolog, AK131315, also binds IRF3 and promotes its activation. More important, AK131315 expression is positively correlated with type I interferon (IFN-I) level and severity in patients with lupus. Mechanistically, in resting cells, IRF3 is bound to suppressor protein Flightless-1 (Fli-1), which keeps its inactive state. Upon infection, IFN-I-induced lncRNA-ISIR binds IRF3 at DNA-binding domain in cytoplasm and removes Fli-1’s association from IRF3, consequently facilitating IRF3 activation. Our results demonstrate that IFN-I-inducible lncRNA-ISIR feedback strengthens IRF3 activation by removing suppressive Fli-1 in immune responses, revealing a method of lncRNA-mediated modulation of transcription factor (TF) activation.
format	article
author	Junfang Xu Pin Wang Zemeng Li Zhiqing Li Dan Han Mingyue Wen Qihang Zhao Lianfeng Zhang Yuanwu Ma Wei Liu Minghong Jiang Xuan Zhang Xuetao Cao
author_facet	Junfang Xu Pin Wang Zemeng Li Zhiqing Li Dan Han Mingyue Wen Qihang Zhao Lianfeng Zhang Yuanwu Ma Wei Liu Minghong Jiang Xuan Zhang Xuetao Cao
author_sort	Junfang Xu
title	IRF3-binding lncRNA-ISIR strengthens interferon production in viral infection and autoinflammation
title_short	IRF3-binding lncRNA-ISIR strengthens interferon production in viral infection and autoinflammation
title_full	IRF3-binding lncRNA-ISIR strengthens interferon production in viral infection and autoinflammation
title_fullStr	IRF3-binding lncRNA-ISIR strengthens interferon production in viral infection and autoinflammation
title_full_unstemmed	IRF3-binding lncRNA-ISIR strengthens interferon production in viral infection and autoinflammation
title_sort	irf3-binding lncrna-isir strengthens interferon production in viral infection and autoinflammation
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/ac0dbf9e59fb4eb680027ce458b31f15
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IRF3-binding lncRNA-ISIR strengthens interferon production in viral infection and autoinflammation

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