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      Gene regulation in the immune system by long noncoding RNAs

      Author(s): , ,
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      Journal: Nature Immunology
      Publisher: Springer Nature

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          Abstract

          Long non-coding RNAs (lncRNAs) are being increasingly appreciated as important regulators of gene expression. Chang and colleagues review the roles identified for lncRNAs in the immune system and discuss models for how lncRNAs mediate their effects.

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          Long noncoding RNA as modular scaffold of histone modification complexes.

          Miao-Chih Tsai, Ohad Manor, Yue Wan … (2010)
          Long intergenic noncoding RNAs (lincRNAs) regulate chromatin states and epigenetic inheritance. Here, we show that the lincRNA HOTAIR serves as a scaffold for at least two distinct histone modification complexes. A 5' domain of HOTAIR binds polycomb repressive complex 2 (PRC2), whereas a 3' domain of HOTAIR binds the LSD1/CoREST/REST complex. The ability to tether two distinct complexes enables RNA-mediated assembly of PRC2 and LSD1 and coordinates targeting of PRC2 and LSD1 to chromatin for coupled histone H3 lysine 27 methylation and lysine 4 demethylation. Our results suggest that lincRNAs may serve as scaffolds by providing binding surfaces to assemble select histone modification enzymes, thereby specifying the pattern of histone modifications on target genes.
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            Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA.

            Sandra S. Diebold, Tsuneyasu Kaisho, Hiroaki Hemmi … (2004)
            Interferons (IFNs) are critical for protection from viral infection, but the pathways linking virus recognition to IFN induction remain poorly understood. Plasmacytoid dendritic cells produce vast amounts of IFN-alpha in response to the wild-type influenza virus. Here, we show that this requires endosomal recognition of influenza genomic RNA and signaling by means of Toll-like receptor 7 (TLR7) and MyD88. Single-stranded RNA (ssRNA) molecules of nonviral origin also induce TLR7-dependent production of inflammatory cytokines. These results identify ssRNA as a ligand for TLR7 and suggest that cells of the innate immune system sense endosomal ssRNA to detect infection by RNA viruses.
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              Ab initio reconstruction of transcriptomes of pluripotent and lineage committed cells reveals gene structures of thousands of lincRNAs

              Mitchell Guttman, Manuel Garber, Joshua Levin … (2010)
              RNA-Seq provides an unbiased way to study a transcriptome, including both coding and non-coding genes. To date, most RNA-Seq studies have critically depended on existing annotations, and thus focused on expression levels and variation in known transcripts. Here, we present Scripture, a method to reconstruct the transcriptome of a mammalian cell using only RNA-Seq reads and the genome sequence. We apply it to mouse embryonic stem cells, neuronal precursor cells, and lung fibroblasts to accurately reconstruct the full-length gene structures for the vast majority of known expressed genes. We identify substantial variation in protein-coding genes, including thousands of novel 5′-start sites, 3′-ends, and internal coding exons. We then determine the gene structures of over a thousand lincRNA and antisense loci. Our results open the way to direct experimental manipulation of thousands of non-coding RNAs, and demonstrate the power of ab initio reconstruction to render a comprehensive picture of mammalian transcriptomes.
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                Author and article information

                Journal
                Title: Nature Immunology
                Abbreviated Title: Nat Immunol
                Publisher: Springer Nature
                ISSN (Print): 1529-2908
                ISSN (Electronic): 1529-2916
                Publication date Created: August 22 2017
                Publication date (Print): August 22 2017
                Volume: 18
                Issue: 9
                Pages: 962-972
                Article
                DOI: 10.1038/ni.3771
                PubMed ID: 28829444
                SO-VID: 579908a0-6fd2-48a2-a0c5-6d5296c405fb
                Copyright © © 2017
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