title: Long non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes.
abstract: Early reports indicate that long non-coding RNAs (lncRNAs) are novel regulators of biological responses. However, their role in the human innate immune response, which provides the initial defence against infection, is largely unexplored. To address this issue, here we characterize the long non-coding RNA transcriptome in primary human monocytes using RNA sequencing. We identify 76 enhancer RNAs (eRNAs), 40 canonical lncRNAs, 65 antisense lncRNAs and 35 regions of bidirectional transcription (RBT) that are differentially expressed in response to bacterial lipopolysaccharide (LPS). Crucially, we demonstrate that knockdown of nuclear-localized, NF-κB-regulated, eRNAs (IL1β-eRNA) and RBT (IL1β-RBT46) surrounding the IL1β locus, attenuates LPS-induced messenger RNA transcription and release of the proinflammatory mediators, IL1β and CXCL8. We predict that lncRNAs can be important regulators of the human innate immune response.
authors.affiliation: 1] CGAT Programme, MRC Functional Genomics Unit, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3QX, UK [2].
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: IIott
authors.affiliation: 1] Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, BA2 7AY Bath, UK [2].
authors.forename: James A
authors.initials: JA
authors.lastname: Heward
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, BA2 7AY Bath, UK.
authors.forename: Benoit
authors.initials: B
authors.lastname: Roux
authors.affiliation: Respiratory Research Group, University Hospital of South Manchester, University of Manchester, Southmoor Road, Manchester M23 9LY, UK.
authors.forename: Eleni
authors.initials: E
authors.lastname: Tsitsiou
authors.affiliation: Airways Disease, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Fenwick
authors.affiliation: Department of Functional and Comparative Genomics, Centre for Genomic Research, University of Liverpool, Liverpool L69 3BX, UK.
authors.forename: Luca
authors.initials: L
authors.lastname: Lenzi
authors.affiliation: Department of Functional and Comparative Genomics, Centre for Genomic Research, University of Liverpool, Liverpool L69 3BX, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Goodhead
authors.affiliation: Department of Functional and Comparative Genomics, Centre for Genomic Research, University of Liverpool, Liverpool L69 3BX, UK.
authors.forename: Christiane
authors.initials: C
authors.lastname: Hertz-Fowler
authors.affiliation: CGAT Programme, MRC Functional Genomics Unit, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3QX, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Heger
authors.affiliation: Department of Functional and Comparative Genomics, Centre for Genomic Research, University of Liverpool, Liverpool L69 3BX, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Hall
authors.affiliation: Airways Disease, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
authors.forename: Louise E
authors.initials: LE
authors.lastname: Donnelly
authors.affiliation: CGAT Programme, MRC Functional Genomics Unit, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3QX, UK.
authors.forename: David
authors.initials: D
authors.lastname: Sims
authors.affiliation: 1] Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, BA2 7AY Bath, UK [2] Respiratory Research Group, University Hospital of South Manchester, University of Manchester, Southmoor Road, Manchester M23 9LY, UK [3] Airways Disease, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lindsay
mesh_terms: D001665:Binding Sites; D004742:Enhancer Elements, Genetic; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012313:RNA / Q000502:physiology*; D062085:RNA, Long Noncoding / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D062085:RNA, Long Noncoding; D012313:RNA