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. Epub 2013 Aug 1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Nucleus / metabolism
  • Cyclooxygenase 2 / genetics
  • Cytokines / genetics
  • Cytokines / metabolism
  • Cytosol / metabolism
  • Gene Expression Regulation*
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism
  • Immunity, Innate / genetics*
  • Inflammation / genetics*
  • Macrophage Activation
  • Macrophages / immunology*
  • Macrophages / metabolism*
  • Mice
  • Models, Immunological
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transcriptional Activation

Substances

  • Cytokines
  • Heterogeneous-Nuclear Ribonucleoproteins
  • RNA, Long Noncoding
  • Toll-Like Receptors
  • Transcription Factors
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2

Associated data

  • GEO/GSE40978