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Cell. 2016 Jun 16;165(7):1672-1685. doi: 10.1016/j.cell.2016.05.075.

A Long Noncoding RNA lincRNA-EPS Acts as a Transcriptional Brake to Restrain Inflammation.

Author information

1
Program in Innate Immunity, University of Massachusetts Medical School, Worcester, MA 01605, USA.
2
Whitehead Institute, Massachusetts Institute of Technology (MIT), Cambridge, MA 02142, USA.
3
Center for Personal Dynamic Regulomes and Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
4
Howard Hughes Medical Institute and Department of Biochemistry and Pharmacology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
5
Program in Innate Immunity, University of Massachusetts Medical School, Worcester, MA 01605, USA; Centre for Molecular Inflammation Research, Department of Cancer Research and Molecular Medicine, NTNU, 7491 Trondheim, Norway. Electronic address: kate.fitzgerald@umassmed.edu.

Abstract

Long intergenic noncoding RNAs (lincRNAs) are important regulators of gene expression. Although lincRNAs are expressed in immune cells, their functions in immunity are largely unexplored. Here, we identify an immunoregulatory lincRNA, lincRNA-EPS, that is precisely regulated in macrophages to control the expression of immune response genes (IRGs). Transcriptome analysis of macrophages from lincRNA-EPS-deficient mice, combined with gain-of-function and rescue experiments, revealed a specific role for this lincRNA in restraining IRG expression. Consistently, lincRNA-EPS-deficient mice manifest enhanced inflammation and lethality following endotoxin challenge in vivo. lincRNA-EPS localizes at regulatory regions of IRGs to control nucleosome positioning and repress transcription. Further, lincRNA-EPS mediates these effects by interacting with heterogeneous nuclear ribonucleoprotein L via a CANACA motif located in its 3' end. Together, these findings identify lincRNA-EPS as a repressor of inflammatory responses, highlighting the importance of lincRNAs in the immune system.

PMID:
27315481
PMCID:
PMC5289747
DOI:
10.1016/j.cell.2016.05.075
[Indexed for MEDLINE]
Free PMC Article

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