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
Medical Subject Headings
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.
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.