ArticleCell2024
Regulation of human interferon signaling by transposon exonization.
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Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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45citing papers in PubMed
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45 citing papers in PubMed.
- Activation of transposable elements is linked to a region- and cell type-specific interferon response in Parkinson's disease.Science advances · 2026Article
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- Gene body methylation suppresses intragenic transcription and permits epigenetic inheritance in a cnidarian.Nature ecology & evolution · 2026Article
- A decoy receptor antagonizes interferon mediated antiviral responses in teleost fish.BMC biology · 2026Article
- Epigenetic lockdown of type I interferon sensing and signalling in human pluripotent cells.Nature communications · 2026Article
- Disease-associated genetic variants can cause missense effects in tissue-specific protein isoforms.Nature communications · 2026Article
- Review
- An ancient retrotransposon provides species-specific tuning of IL-18 inflammatory signaling.bioRxiv : the preprint server for biology · 2026Article
- Longitudinal Repeatome Remodeling in Peripheral Blood Following Parkinson's Disease Diagnosis.Genes · 2026Article
- Pseudogene revival drives repeated adaptation in fission yeast.Molecular biology and evolution · 2026Article
- Long-read assembly reveals vast transcriptional complexity in the placenta associated with metabolic and endocrine function.Nature communications · 2026Article
- Transposable element-gene chimera cartography, origination and role in enhancing transcriptome plasticity.Nature structural & molecular biology · 2026Article
- The splice of life: how alternative splicing shapes regulatory and phenotypic evolution.The EMBO journal · 2026Review
- Macrophage retrotransposon expression is associated with lupus.Genes and immunity · 2026Article
- Architectural and evolutionary features of TE-derived TSSs shape tissue-specific promoter activity in the human genome.Nature communications · 2026Article
- Expression spectrum of TE-driven transcripts in human adult tissues.Genome biology · 2026Article
- Polymorphic 3D genome architecture mediated by transposable elements.bioRxiv : the preprint server for biology · 2026Article
- Locus-specific HERV expression identifies an aggressive, NK-depleted, checkpoint-refractory acral melanoma phenotype.Frontiers in medicine · 2026Article
- Transposable elements as a possible missing link between genetic predisposition and environmental triggers of autoimmune disorders: insights from type 1 diabetes, systemic lupus erythematosus and rheumatoid arthritis.Frontiers in immunology · 2026Review
Corrections and comments
- Update of
Authors and funding
17 authors.
Giulia Irene Maria PasquesiBioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA; Crnic Institute Boulder Branch, BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80303, USA.
Holly AllenBioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA.
Atma IvancevicBioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA.
Arturo Barbachano-GuerreroBioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA.
Olivia JoynerBioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA.
Kejun GuoDivision of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
David M SimpsonBioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA.
Keala GapinBioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA.
Isabella HortonBioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA.
Lily L NguyenBioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA; Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Qing YangBioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA; Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
Cody J WarrenBioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA; The Ohio State University College of Veterinary Medicine, Columbus, OH 43210, USA.
Liliana D FloreaMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Benjamin G BitlerDivision of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Mario L SantiagoDivision of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Sara L SawyerBioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA.
Edward B ChuongBioFrontiers Institute and Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO 80309, USA; Crnic Institute Boulder Branch, BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80303, USA. Electronic address: edward.chuong@colorado.edu.
Funding
University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0MBreaking the Barrier to an HIV VaccineDP1AI175471 · NIAID · UNIVERSITY OF COLORADO · PI Sara Sawyer · 2022 to 2026
$5.5MCharacterizing Host-Virus Interactions in a New HIV Model OrganismR01OD034046 · OD · UNIVERSITY OF COLORADO · PI Sara Sawyer · 2022 to 2026
$3.6MPredoctoral Training Program in Signaling and Cellular Regulation INCLUDE Down Syndrome SupplementT32GM142607 · NIGMS · UNIVERSITY OF COLORADO · PI Sabrina Leigh Spencer, Tin Tin Su · 2021 to 2026
$3.6MTransposon-mediated rewiring of gene regulatory networksR35GM128822 · NIGMS · UNIVERSITY OF COLORADO · PI Edward Bo-yi Chuong · 2018 to 2026
$3.5MRole of Type I IFNs in Mucosal HIV-1 Immunity and PathogenesisR01AI134220 · NIAID · UNIVERSITY OF COLORADO DENVER · PI SANTIAGO, MARIO LUIS, WILSON, CARA C. · 2017 to 2021
$2.7MTargeting Wnt signaling in therapy-resistant ovarian cancerR37CA261987 · NCI · UNIVERSITY OF COLORADO DENVER · PI Benjamin G Bitler · 2021 to 2026
$2.4MComputational Methods to Characterize Alternative Splicing from Massive Collections of RNA-seq DataR01GM129085 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI FLOREA, LILIANA D · 2019 to 2022
$1.5MFACSAria Fusion Cell SorterS10OD021601 · OD · UNIVERSITY OF COLORADO · PI LIU, XUEDONG · 2016 to 2016
$599kIdentifying genetic barriers to animal virus replication in human cells: Insights into zoonosisR00AI151256 · NIAID · OHIO STATE UNIVERSITY · PI WARREN, CODY JAY · 2023 to 2024
$493kUnderstanding how transposons generate new immune gene protein-coding splice variantsK99GM152820 · NIGMS · UNIVERSITY OF COLORADO · PI PASQUESI, GIULIA IRENE MARIA · 2024 to 2025
$250kIdentifying genetic barriers to animal virus replication in human cells: Insights into zoonosisK99AI151256 · NIAID · UNIVERSITY OF COLORADO · PI WARREN, CODY JAY · 2021 to 2022
$118kNCI NIH HHS P30 CA046934NCI NIH HHS R37 CA261987NIAID NIH HHS DP1 AI175471NIAID NIH HHS K99 AI151256NIAID NIH HHS R00 AI151256NIAID NIH HHS R01 AI134220NIGMS NIH HHS K99 GM152820NIGMS NIH HHS R01 GM129085NIGMS NIH HHS R35 GM128822NIGMS NIH HHS T32 GM142607NIH HHS R01 OD034046NIH HHS S10 OD021601
Abstract
Innate immune signaling is essential for clearing pathogens and damaged cells and must be tightly regulated to avoid excessive inflammation or autoimmunity. Here, we found that the alternative splicing of exons derived from transposable elements is a key mechanism controlling immune signaling in human cells. By analyzing long-read transcriptome datasets, we identified numerous transposon exonization events predicted to generate functional protein variants of immune genes, including the type I interferon receptor IFNAR2. We demonstrated that the transposon-derived isoform of IFNAR2 is more highly expressed than the canonical isoform in almost all tissues and functions as a decoy receptor that potently inhibits interferon signaling, including in cells infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our findings uncover a primate-specific axis controlling interferon signaling and show how a transposon exonization event can be co-opted for immune regulation.
Indexed as
Alternative SplicingDNA Transposable ElementsExonsReceptor, Interferon alpha-betaSARS-CoV-2Signal TransductionAnimalsCOVID-19HEK293 CellsHumansImmunity, InnateInterferonsProtein IsoformsDNA Transposable ElementsIFNAR2 protein, humanInterferonsProtein IsoformsReceptor, Interferon alpha-betaalternative splicinginnate immunitytransposable elementstype I IFN
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