Long noncoding RNA CHROMR regulates antiviral immunity in humans

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 119; no. 37; pp. 1 - 9
• Main Authors: van Solingen, Coen, Cyr, Yannick, Scacalossi, Kaitlyn R., deVries, Maren, Barrett, Tessa J., de Jong, Annika, Gourvest, Morgane, Zhang, Tracy, Peled, Daniel, Kher, Raadhika, Cornwell, MacIntosh, Gildea, Michael A., Brown, Emily J., Fanucchi, Stephanie, Mhlanga, Musa M., Berger, Jeffrey S., Dittmann, Meike, Moore, Kathryn J.
• Format: Journal Article
• Language: English
• Published: Washington National Academy of Sciences 13.09.2022
• Subjects: Acetylation; Arbitration; Biological Sciences; Depletion; Gene expression; Histones; Immunity; Immunoregulation; Influenza A; Interferon; Interferon regulatory factor; Macrophages; Microorganisms; Non-coding RNA; Regulatory sequences; Severe acute respiratory syndrome coronavirus 2; Signaling; Viral diseases
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2210321119

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.