A long noncoding RNA induced by TLRs mediates both activation and repression of immune response genes

By Susan B. Carpenter, Maninjay K. Atianand, Daniela Aiello, Emiliano P. Ricci, Pallavi Gandhi, Lisa L. Hall, M. Byron, Brian G. Monks, Meabh Henry-Bezy, Luke A. O'Neill and 4 more. Science, 2013

885 citations recorded by the source corpus.

A New Linc in Innate Immunity Long noncoding RNAs (lncRNAs) have recently emerged as important regulators of gene expression in a wide variety of biological processes, although specific roles for these molecules in the immune system have not been described. Carpenter et al. (p. 789, published online 1 August) now define the function of one such lncRNA in the immune system, lincRNA-Cox2. Whole-transcriptome profiling revealed that lincRNA-Cox2 was induced in mouse macrophages in response to activation of Toll-like receptors—molecules that detect microbes and alert the immune system to respond. LincRNA-Cox2 both positively and negatively regulated the expression of distinct groups of inflammatory genes. Negative regulation of gene expression was mediated by lincRNA-Cox interaction with heterogeneous nuclear ribonucleoprotein A/B and A2/B1. In mice, a broadly acting RNA, lincRNA-Cox2, regulates the circuit that controls the inflammatory response. 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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/59e2253cfaaeb338590a0eb53b91f1f9a3c36039

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Citations in the corpus

Molecular Mechanisms That Influence the Macrophage M1–M2 Polarization Balance (2014, background): “A novel class of large intergenic non-coding RNAs, termed as lincRNAs, has been recently shown to be involved in both activation and repression of immune response genes (111).”
Localization and abundance analysis of human lncRNAs at single-cell and single-molecule resolution (2015, background): “More recently, researchers have developed and applied single molecule RNA FISH techniques based on hybridization of multiple short, fluorescently labeled, oligonucleotide probes [23,24] to estimate the absolute level and subcellular localization of even low abundance lncRNAs [8,25-31].”