Genetic Models Reveal cis and trans Immune-Regulatory Activities for lincRNA-Cox2
Fitzgerald, Katherine A.
UMass Chan AffiliationsGraduate School of Biomedical Sciences
Program in Innate Immunity, Department of Medicine, Division of Infectious Diseases and Immunology
Document TypeJournal Article
Genetics and Genomics
Nucleic Acids, Nucleotides, and Nucleosides
MetadataShow full item record
AbstractAn 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.
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
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/40859
Full author list omitted for brevity. For the full list of authors, see article.
RightsThis is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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/).