Genetic models reveal cis and trans immune-regulatory activities for lincRNA-Cox2

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

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Cell reports. - 25, 6 (2018) , 1511-1524.e6, ISSN: 2211-1247

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2019
• Creator: Robinson, Elektra K. ; Shapleigh, Barbara ; Liapis, Stephen C. ; Covarrubias, Sergio ; Katzman, Sol ; Groff, Abigail F. ; Jiang, Zhaozhao ; Agarwal, Shiuli ; Motwani, Mona ; Chan, Jennie ; Sharma, Shruti ; Hennessy, Elizabeth J. ; FitzGerald, Garret A. ; McManus, Michael T. ; Rinn, John L. ; Fitzgerald, Katherine A. ; Carpenter, Susan

Further information

• DOI: 10.1016/j.celrep.2018.10.027
• URN: urn:nbn:de:bsz:25-freidok-1480155
• Rights: Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:43 PM CET