UMMS Affiliation

Program in Innate Immunity, Department of Medicine, Division of Infectious Diseases and Immunology; Graduate School of Biomedical Sciences

Publication Date

2018-11-06

Document Type

Article

Disciplines

Genetic Phenomena | Genetics and Genomics | Immunity | Nucleic Acids, Nucleotides, and Nucleosides

Abstract

An inducible gene expression program is a hallmark of the host inflammatory response. Recently, long intergenic non-coding RNAs (lincRNAs) have been shown to regulate the magnitude, duration, and resolution of these responses. Among these is lincRNA-Cox2, a dynamically regulated gene that broadly controls immune gene expression. To evaluate the in vivo functions of this lincRNA, we characterized multiple models of lincRNA-Cox2-deficient mice. LincRNA-Cox2-deficient macrophages and murine tissues had altered expression of inflammatory genes. Transcriptomic studies from various tissues revealed that deletion of the lincRNA-Cox2 locus also strongly impaired the basal and inducible expression of the neighboring gene prostaglandin-endoperoxide synthase (Ptgs2), encoding cyclooxygenase-2, a key enzyme in the prostaglandin biosynthesis pathway. By utilizing different genetic manipulations in vitro and in vivo, we found that lincRNA-Cox2 functions through an enhancer RNA mechanism to regulate Ptgs2. More importantly, lincRNA-Cox2 also functions in trans, independently of Ptgs2, to regulate critical innate immune genes in vivo.

Keywords

CRISPR/Cas9, CRISPRi, Ptgs2, inflammation, innate immunity, lincRNA-Cox2

Rights and Permissions

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI of Published Version

10.1016/j.celrep.2018.10.027

Source

Cell Rep. 2018 Nov 6;25(6):1511-1524.e6. doi: 10.1016/j.celrep.2018.10.027. Link to article on publisher's site

Journal/Book/Conference Title

Cell reports

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

30404006

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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