Genetic Models Reveal cis and trans Immune-Regulatory Activities for lincRNA-Cox2
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Authors
Elling, RolandJiang, Zhaozhao
Agarwal, Shiuli
Motwani, Mona
Chan, Jennie
Sharma, Shrutie
Fitzgerald, Katherine A.
Carpenter, Susan
UMass Chan Affiliations
Graduate School of Biomedical SciencesProgram in Innate Immunity, Department of Medicine, Division of Infectious Diseases and Immunology
Document Type
Journal ArticlePublication Date
2018-11-06Keywords
CRISPR/Cas9CRISPRi
Ptgs2
inflammation
innate immunity
lincRNA-Cox2
Genetic Phenomena
Genetics and Genomics
Immunity
Nucleic Acids, Nucleotides, and Nucleosides
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Show full item recordAbstract
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.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
DOI
10.1016/j.celrep.2018.10.027Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40859PubMed ID
30404006Notes
Full author list omitted for brevity. For the full list of authors, see article.
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Rights
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2018.10.027
Scopus Count
Except where otherwise noted, this item's license is described as This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).