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Long noncoding RNA CHROMR regulates antiviral immunity in humans

by van Solingen, Coen , Gildea, Michael A. , Fanucchi, Stephanie , Kher, Raadhika , Mhlanga, Musa M. , Zhang, Tracy , Dittmann, Meike , deVries, Maren , Peled, Daniel , Moore, Kathryn J. , Barrett, Tessa J. , de Jong, Annika , Gourvest, Morgane , Scacalossi, Kaitlyn R. , Brown, Emily J. , Berger, Jeffrey S. , Cyr, Yannick , Cornwell, MacIntosh

in Acetylation / Arbitration / Biological Sciences / COVID-19 - genetics / COVID-19 - immunology / Depletion / DNA-Binding Proteins - metabolism / Gene expression / Histones / Humans / Immunity / Immunity, Innate - genetics / Immunology and Inflammation / Immunoregulation / Influenza A / Influenza A virus - immunology / Influenza, Human - genetics / Influenza, Human - immunology / Interferon / Interferon regulatory factor / Interferon Regulatory Factors - genetics / Interferon Regulatory Factors - metabolism / Macrophages / Microorganisms / Non-coding RNA / Regulatory sequences / RNA, Long Noncoding - genetics / RNA, Long Noncoding - physiology / SARS-CoV-2 - immunology / Severe acute respiratory syndrome coronavirus 2 / Signaling / Transcription Factors - metabolism / Viral diseases

2022

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2022

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2022

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Journal Article

Long noncoding RNA CHROMR regulates antiviral immunity in humans

van Solingen, Coen,

Gildea, Michael A.,

Fanucchi, Stephanie,

Kher, Raadhika,

Mhlanga, Musa M.,

Zhang, Tracy,

Dittmann, Meike,

deVries, Maren,

Peled, Daniel,

Moore, Kathryn J.,

Barrett, Tessa J.,

de Jong, Annika,

Gourvest, Morgane,

Scacalossi, Kaitlyn R.,

Brown, Emily J.,

Berger, Jeffrey S.,

Cyr, Yannick,

Cornwell, MacIntosh

2022

Overview

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 IncRNA 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.

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Publisher

National Academy of Sciences

Subject

Acetylation

/ Arbitration

/ Biological Sciences

/ COVID-19 - genetics

/ COVID-19 - immunology

/ Depletion

/ DNA-Binding Proteins - metabolism