Long non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes

Nicholas E. Ilott, James A. Heward, Benoit Roux, Eleni Tsitsiou, Peter S. Fenwick, Luca Lenzi, Ian Goodhead, Christiane Hertz-Fowler, Andreas Heger, Neil Hall, Louise E. Donnelly, David Sims () and Mark A. Lindsay ()
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Nicholas E. Ilott: CGAT Programme, MRC Functional Genomics Unit, Anatomy, and Genetics, University of Oxford
James A. Heward: University of Bath
Benoit Roux: University of Bath
Eleni Tsitsiou: Respiratory Research Group, University Hospital of South Manchester, University of Manchester
Peter S. Fenwick: Airways Disease, National Heart and Lung Institute, Imperial College
Luca Lenzi: Centre for Genomic Research, University of Liverpool
Ian Goodhead: Centre for Genomic Research, University of Liverpool
Christiane Hertz-Fowler: Centre for Genomic Research, University of Liverpool
Andreas Heger: CGAT Programme, MRC Functional Genomics Unit, Anatomy, and Genetics, University of Oxford
Neil Hall: Centre for Genomic Research, University of Liverpool
Louise E. Donnelly: Airways Disease, National Heart and Lung Institute, Imperial College
David Sims: CGAT Programme, MRC Functional Genomics Unit, Anatomy, and Genetics, University of Oxford
Mark A. Lindsay: University of Bath

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms4979

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