NeST, a long noncoding RNA, controls microbial susceptibility and epigenetic activation of the Ifng locus
By J. A. Gomez, Orly L. Wapinski, Yul W. Yang, Jean-François Bureau, Smita Gopinath, D. Monack, Howard Y. Chang, M. Brahic, K. Kirkegaard. Cell, 2013
650 citations recorded by the source corpus.
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 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 methytransferase complex, and to alter histone 3 methylation at the interferon gamma locus. Thus, this lncRNA regulates epigenetic marking of IFNγ-encoding chromatin, expression of IFN-γ and susceptibility to a viral and a bacterial pathogen.
Subfields: Cancer Research, Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/9dd8031a4f7ddfc075148dca94a0b1bef9f4afe2
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Citations in the corpus
- Interferon-Stimulated Genes: A Complex Web of Host Defenses (2014, background): “Recently, and for the first time, a lncRNA was shown to play a critical role in conferring resistance to persistent virus infection (236).”
- Multiple knockout mouse models reveal lincRNAs are required for life and brain development (2013, background): “, Xist, H19, Kcn11ot1, Malat1) (Anguera et al., 2011; Gomez et al., 2013; Gordon et al., 2010; Moseley et al., 2006; Nakagawa et al., 2011; Ripoche et al., 1997; Zhang et al., 2012), leaving the more recent large-scale RNA-Seq-derived catalogs of lincRNAs largely unexplored.”