The NeST Long ncRNA Controls Microbial Susceptibility and Epigenetic Activation of the Interferon-γ Locus

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell (Impact Factor: 32.24). 02/2013; 152(4):743-54. DOI: 10.1016/j.cell.2013.01.015
Source: PubMed


Long noncoding RNAs (lncRNAs) are increasingly appreciated as regulators of cell-specific gene expression. Here, an enhancer-like lncRNA termed NeST (nettoie Salmonella pas Theiler's [cleanup Salmonella not Theiler's]) is shown to be causal for all phenotypes conferred by murine viral susceptibility locus Tmevp3. This locus was defined by crosses between SJL/J and B10.S mice and contains several candidate genes, including NeST. The SJL/J-derived locus confers higher lncRNA expression, increased interferon-γ (IFN-γ) abundance in activated CD8(+) T cells, increased Theiler's virus persistence, and decreased Salmonella enterica pathogenesis. Transgenic expression of NeST lncRNA alone was sufficient to confer all phenotypes of the SJL/J locus. NeST RNA was found to bind WDR5, a component of the histone H3 lysine 4 methyltransferase complex, and to alter histone 3 methylation at the IFN-γ locus. Thus, this lncRNA regulates epigenetic marking of IFN-γ-encoding chromatin, expression of IFN-γ, and susceptibility to a viral and a bacterial pathogen.

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Available from: Jean-François Bureau, Aug 29, 2015
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    • "Underscoring the functional importance of RNA binding activity, it was further shown that mouse ESCs expressing an RNA-bindingdeficient WDR5 were compromised for maintaining their stem cell fate. Another example of a physiologically relevant WDR5-lncRNA interaction came from a study looking into the role of the lncRNA NeST (Gomez et al., 2013). In mouse CD8 + T cells, this lncRNA was suggested to bind WDR5 and upregulate interferon-γ. "
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