title: Cutting Edge: A Natural Antisense Transcript, AS-IL1α, Controls Inducible Transcription of the Proinflammatory Cytokine IL-1α.
abstract: Natural antisense transcripts (NATs) are a class of long noncoding RNAs (lncRNAs) that are complementary to other protein-coding genes. Although thousands of NATs are encoded by mammalian genomes, their functions in innate immunity are unknown. In this study, we identified and characterized a novel NAT, AS-IL1α, which is partially complementary to IL-1α. Similar to IL-1α, AS-IL1α is expressed at low levels in resting macrophages and is induced following infection with Listeria monocytogenes or stimulation with TLR ligands (Pam3CSK4, LPS, polyinosinic-polycytidylic acid). Inducible expression of IL-1α mRNA and protein were significantly reduced in macrophages expressing shRNA that target AS-IL1α. AS-IL1α is located in the nucleus and did not alter the stability of IL-1α mRNA. Instead, AS-IL1α was required for the recruitment of RNA polymerase II to the IL-1α promoter. In summary, our studies identify AS-IL1α as an important regulator of IL-1α transcription during the innate immune response.
authors.affiliation: Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605;
authors.forename: Jennie
authors.initials: J
authors.lastname: Chan
authors.affiliation: Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605;
authors.forename: Maninjay
authors.initials: M
authors.lastname: Atianand
authors.affiliation: Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605;
authors.forename: Zhaozhao
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605; Department of Immunology and Microbiology, University of California, San Francisco, San Francisco, CA 94143; and.
authors.forename: Susan
authors.initials: S
authors.lastname: Carpenter
authors.affiliation: Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605;
authors.forename: Daniel
authors.initials: D
authors.lastname: Aiello
authors.affiliation: Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605;
authors.forename: Roland
authors.initials: R
authors.lastname: Elling
authors.affiliation: Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605; Centre for Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, 7491 Trondheim, Norway Kate.Fitzgerald@umassmed.edu Daniel.Caffrey@umassmed.edu.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Fitzgerald
authors.affiliation: Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605; Kate.Fitzgerald@umassmed.edu Daniel.Caffrey@umassmed.edu.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Caffrey
mesh_terms: D000818:Animals; D002460:Cell Line; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D056426:Genetic Loci; D018836:Inflammation Mediators; D053582:Interleukin-1alpha / Q000235:genetics*; D008024:Ligands; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D034622:RNA Interference; D016372:RNA, Antisense / Q000235:genetics*; D022661:RNA, Untranslated / Q000235:genetics*; D051193:Toll-Like Receptors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D008024:Ligands; D016328:NF-kappa B; D016372:RNA, Antisense; D022661:RNA, Untranslated; D051193:Toll-Like Receptors