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

Maninjay K. Atianand, Wenqian Hu, Ansuman T. Satpathy, Ying Shen, Emiliano P. Ricci, Juan R. Alvarez-Dominguez, Ankit Bhatta, Stefan A. Schattgen, Jason D. McGowan, Juliana Blin, Joerg E. Braun, Pallavi Gandhi, Melissa J. Moore, Howard Y. Chang, Harvey F. Lodish, Daniel R. Caffrey, Katherine A. Fitzgerald

Research output: Contribution to journalArticlepeer-review

203 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1672-1685
Number of pages14
JournalCell
Volume165
Issue number7
DOIs
StatePublished - Jun 16 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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