ArticleProceedings of the National Academy of Sciences of the United States of America2022
Single-cell RNA sequencing uncovers the nuclear decoy lincRNA PIRAT as a regulator of systemic monocyte immunity during COVID-19.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 38 citations in OpenAlex.
- Single-cell RNA sequencing data analysis reveals differential expressions of ion channels in immunity response to pulmonary COVID-19 infection.Biochemical and biophysical research communications · 2026Article
- Functional Genomic Screening Identifies lncRNA CNPY2-AS1 as a Regulator of Redox Metabolism and Antiviral Immunity.International journal of biological sciences · 2026Article
- CYP1B1-AS1 regulates CYP1B1 to promote Coxiella burnetii pathogenesis by inhibiting ROS and host cell death.Nature communications · 2025Article
- A searchable atlas of pathogen-sensitive lncRNA networks in human macrophages.Nature communications · 2025Article
- Single-cell transcriptomic characterization of microscopic colitis.Nature communications · 2025Article
- What's in a name: the multifaceted function of DNA- and RNA-binding proteins in T cell responses.The FEBS journal · 2025Review
- Genetic Variants in Genes Related to Lung Function and Interstitial Lung Diseases Are Associated with Worse Outcomes in Severe COVID-19 and Lung Performance in the Post-COVID-19 Condition.International journal of molecular sciences · 2025Article
- Non-coding RNA Networks in Infection.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Non-coding RNAs in the viral host-pathogen interaction: molecular regulation and therapeutic potential.Frontiers in cellular and infection microbiology · 2025Review
- Unveiling Long Non-coding RNA Networks from Single-Cell Omics Data Through Artificial Intelligence.Methods in molecular biology (Clifton, N.J.) · 2025Article
- RUNX1 interacts with lncRNA SMANTIS to regulate monocytic cell functions.Communications biology · 2024Article
- The pseudogene GBP1P1 suppresses influenza A virus replication by acting as a protein decoy for DHX9.Journal of virology · 2024Article
- Approaches to probe and perturb long noncoding RNA functions in diseases.Current opinion in genetics & development · 2024Review
- Unveiling the Hidden Regulators: The Impact of lncRNAs on Zoonoses.International journal of molecular sciences · 2024Review
- Stimulation of PSTPIP1 to trigger proinflammatory responses in asymptomatic SARS-CoV-2 infections.Heliyon · 2024Article
- Bulk and Single-Cell RNA Sequencing Elucidate the Etiology of Severe COVID-19.International journal of molecular sciences · 2024Review
- Non-coding RNAs in disease: from mechanisms to therapeutics.Nature reviews. Genetics · 2024Review
- Cell-specific housekeeping role of lncRNAs in COVID-19-infected and recovered patients.NAR genomics and bioinformatics · 2024Article
- Epigenetic regulation of pulmonary inflammation.Seminars in cell & developmental biology · 2024Review
- EVLncRNAs 3.0: an updated comprehensive database for manually curated functional long non-coding RNAs validated by low-throughput experiments.Nucleic acids research · 2024Article
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Authors and funding
27 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The systemic immune response to viral infection is shaped by master transcription factors, such as NF-κB, STAT1, or PU.1. Although long noncoding RNAs (lncRNAs) have been suggested as important regulators of transcription factor activity, their contributions to the systemic immunopathologies observed during SARS-CoV-2 infection have remained unknown. Here, we employed a targeted single-cell RNA sequencing approach to reveal lncRNAs differentially expressed in blood leukocytes during severe COVID-19. Our results uncover the lncRNA PIRAT (PU.1-induced regulator of alarmin transcription) as a major PU.1 feedback-regulator in monocytes, governing the production of the alarmins S100A8/A9, key drivers of COVID-19 pathogenesis. Knockout and transgene expression, combined with chromatin-occupancy profiling, characterized PIRAT as a nuclear decoy RNA, keeping PU.1 from binding to alarmin promoters and promoting its binding to pseudogenes in naïve monocytes. NF-κB-dependent PIRAT down-regulation during COVID-19 consequently releases a transcriptional brake, fueling alarmin production. Alarmin expression is additionally enhanced by the up-regulation of the lncRNA LUCAT1, which promotes NF-κB-dependent gene expression at the expense of targets of the JAK-STAT pathway. Our results suggest a major role of nuclear noncoding RNA networks in systemic antiviral responses to SARS-CoV-2 in humans.
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