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A Long Noncoding RNA Mediates Both Activation and Repression of Immune Response Genes

Science  16 Aug 2013:
Vol. 341, Issue 6147, pp. 789-792
DOI: 10.1126/science.1240925

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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.

Abstract

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.

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