Long noncoding RNA <i>CHROMR</i> regulates antiviral immunity in humans.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36001732.
- Also identified by DOI 10.1073/pnas.2210321119 and PMC identifier 9477407.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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 <i>CHROMR</i> is induced by influenza A virus and SARS-CoV-2 infection and coordinates the expression of interferon-stimulated genes (ISGs) that execute antiviral responses. <i>CHROMR</i> 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 <i>CHROMR</i> sequesters the interferon regulatory factor (IRF)-2-dependent transcriptional corepressor IRF2BP2, thereby licensing IRF-dependent signaling and transcription of the ISG network. Consequently, <i>CHROMR</i> expression is essential to restrict viral infection of macrophages. Our findings identify <i>CHROMR</i> as a key arbitrator of antiviral innate immune signaling in humans.
Medical subject headings
- COVID-19
- DNA-Binding Proteins
- Immunity, Innate
- Influenza A virus
- Influenza, Human
- RNA, Long Noncoding
- SARS-CoV-2
- Transcription Factors