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

IIott, NE; Heward, JA; Roux, B; Tsitsiou, E; Fenwick, PS; Lenzi, L; Goodhead, IB; Hertz-Fowler, C; Heger, A; Hall, N; Donnelly, LE; Sims, D; Lindsay, MA

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


Authors

NE IIott

JA Heward

B Roux

E Tsitsiou

PS Fenwick

L Lenzi

C Hertz-Fowler

A Heger

N Hall

LE Donnelly

D Sims

MA Lindsay



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.

Citation

IIott, N., Heward, J., Roux, B., Tsitsiou, E., Fenwick, P., Lenzi, L., …Lindsay, M. (2014). Long non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes. Nature communications, 5, 3979-3979. https://doi.org/10.1038/ncomms4979

Journal Article Type Article
Acceptance Date Apr 29, 2014
Publication Date Jun 9, 2014
Deposit Date Sep 23, 2015
Publicly Available Date Apr 5, 2016
Journal Nature Communications
Print ISSN 2041-1723
Electronic ISSN 2041-1723
Peer Reviewed Peer Reviewed
Volume 5
Pages 3979-3979
DOI https://doi.org/10.1038/ncomms4979
Publisher URL http://dx.doi.org/10.1038/ncomms4979
Related Public URLs http://www.nature.com/ncomms/index.html
Additional Information Funders : Biotechnology and Biosciences Sciences Research Council (BBSRC);Medical Research Council (MRC)

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