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标题：Long noncoding RNA CHROMR regulates antiviral immunity in humans
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作者：Coen van Solingen ; Yannick Cyr ; Kaitlyn R. Scacalossi 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2022
卷号：119
期号：37
DOI：10.1073/pnas.2210321119
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance An effective innate immune response to virus infection requires the induction of type I interferons and up-regulation of hundreds of interferon-stimulated genes (ISGs) that instruct antiviral functions and immune regulation. Deciphering the regulatory mechanisms that direct expression of the ISG network is critical for understanding the fundamental organization of the innate immune response and the development of antiviral therapies. We define a regulatory role for the primate-specific long noncoding RNA CHROMR in coordinating ISG transcription. CHROMR sequesters the interferon regulatory factor (IRF)-2/IRF2BP2 complex that restrains ISG transcription and thus is required to restrict influenza virus replication. These data identify a novel regulator of the antiviral gene program in humans and provide insights into the multilayered regulatory network that controls the innate immune response. Long noncoding RNAs (lncRNAs) have emerged as critical regulators of gene expression, yet their contribution to immune regulation in humans remains poorly understood. Here, we report that the primate-specific lncRNA CHROMR is induced by influenza A virus and SARS-CoV-2 infection and coordinates the expression of interferon-stimulated genes (ISGs) that execute antiviral responses. CHROMR depletion in human macrophages reduces histone acetylation at regulatory regions of ISG loci and attenuates ISG expression in response to microbial stimuli. Mechanistically, we show that CHROMR sequesters the interferon regulatory factor (IRF)-2-dependent transcriptional corepressor IRF2BP2, thereby licensing IRF-dependent signaling and transcription of the ISG network. Consequently, CHROMR expression is essential to restrict viral infection of macrophages. Our findings identify CHROMR as a key arbitrator of antiviral innate immune signaling in humans.
关键词：enlncRNAinnate immune signalinginterferon-stimulated genesantiviral response