Long noncoding RNA CHROMR regulates antiviral immunity in humans.
Coen van SolingenYannick CyrKaitlyn R ScacalossiMaren de VriesTessa J BarrettAnnika de JongMorgane GourvestTracy ZhangDaniel PeledRaadhika KherMacIntosh Grant CornwellMichael A GildeaEmily J BrownStephanie FanucchiMusa M MhlangaJeffrey S BergerMeike DittmannKatherine MoorePublished in: Proceedings of the National Academy of Sciences of the United States of America (2022)
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.
Keyphrases
- long noncoding rna
- poor prognosis
- gene expression
- dendritic cells
- transcription factor
- innate immune
- dna methylation
- long non coding rna
- genome wide
- binding protein
- immune response
- microbial community
- oxidative stress
- sars cov
- genome wide identification
- network analysis
- respiratory syndrome coronavirus
- heat shock protein