A long noncoding RNA mediates both activation and repression of immune response genes
Department of Medicine, Division of Infectious Diseases and Immunology; Department of Cell and Developmental Biology; Department of Biochemistry and Molecular Pharmacology
Animals; Cell Line; Cell Nucleus; Cyclooxygenase 2; Cytokines; Cytosol; *Gene Expression Regulation; Heterogeneous-Nuclear Ribonucleoproteins; Immunity, Innate; Inflammation; Macrophage Activation; Macrophages; Mice; Models, Immunological; RNA Interference; RNA, Long Noncoding; Toll-Like Receptors; Transcription Factors; Transcription, Genetic; Transcriptional Activation
Immunity | Immunology and Infectious Disease | Molecular Genetics
An inducible program of inflammatory gene expression is central to antimicrobial defenses. This response is controlled by a collaboration involving signal-dependent activation of transcription factors, transcriptional co-regulators, and chromatin-modifying factors. We have identified a long noncoding RNA (lncRNA) that acts as a key regulator of this inflammatory response. Pattern recognition receptors such as the Toll-like receptors induce the expression of numerous lncRNAs. One of these, lincRNA-Cox2, mediates both the activation and repression of distinct classes of immune genes. Transcriptional repression of target genes is dependent on interactions of lincRNA-Cox2 with heterogeneous nuclear ribonucleoprotein A/B and A2/B1. Collectively, these studies unveil a central role of lincRNA-Cox2 as a broad-acting regulatory component of the circuit that controls the inflammatory response.
DOI of Published Version
Carpenter S, Aiello D, Atianand MK, Ricci EP, Gandhi P, Hall LL, Byron M, Monks B, Henry-Bezy M, Lawrence JB, O'Neill LA, Moore MJ, Caffrey DR, Fitzgerald KA. A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013 Aug 16;341(6147):789-92. doi:10.1126/science.1240925. Link to article on publisher's site
Science (New York, N.Y.)
Carpenter, Susan; Aiello, Daniel; Atianand, Maninjay K.; Ricci, Emiliano P.; Gandhi, Pallavi; Hall, Lisa L.; Byron, Meg; Monks, Brian G.; Henry-Bezy, Meabh; Lawrence, Jeanne B.; O'Neill, Luke A. J.; Moore, Melissa J.; Caffrey, Daniel R.; and Fitzgerald, Katherine A., "A long noncoding RNA mediates both activation and repression of immune response genes" (2013). Lawrence Lab Publications. 13.