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The Ro60 autoantigen binds endogenous retroelements and regulates inflammatory gene expression.
Hung, T; Pratt, G A; Sundararaman, B; Townsend, M J; Chaivorapol, C; Bhangale, T; Graham, R R; Ortmann, W; Criswell, L A; Yeo, G W; Behrens, T W.
Affiliation
  • Hung T; Genentech, South San Francisco, CA 94080, USA. behrens.tim@gene.com hungt2@gene.com geneyeo@ucsd.edu.
  • Pratt GA; Department of Cellular and Molecular Medicine, Institute for Genomic Medicine, Stem Cell Program, University of California at San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA.
  • Sundararaman B; Department of Cellular and Molecular Medicine, Institute for Genomic Medicine, Stem Cell Program, University of California at San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA.
  • Townsend MJ; Genentech, South San Francisco, CA 94080, USA.
  • Chaivorapol C; Genentech, South San Francisco, CA 94080, USA.
  • Bhangale T; Genentech, South San Francisco, CA 94080, USA.
  • Graham RR; Genentech, South San Francisco, CA 94080, USA.
  • Ortmann W; Genentech, South San Francisco, CA 94080, USA.
  • Criswell LA; Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center, University of California, San Francisco, CA 94143, USA.
  • Yeo GW; Department of Cellular and Molecular Medicine, Institute for Genomic Medicine, Stem Cell Program, University of California at San Diego, Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA. Department of Physiology, National University of Singapore,
  • Behrens TW; Genentech, South San Francisco, CA 94080, USA. behrens.tim@gene.com hungt2@gene.com geneyeo@ucsd.edu.
Science ; 350(6259): 455-9, 2015 Oct 23.
Article in En | MEDLINE | ID: mdl-26382853
ABSTRACT
Autoantibodies target the RNA binding protein Ro60 in systemic lupus erythematosus (SLE) and Sjögren's syndrome. However, it is unclear whether Ro60 and its associated RNAs contribute to disease pathogenesis. We catalogued the Ro60-associated RNAs in human cell lines and found that among other RNAs, Ro60 bound an RNA motif derived from endogenous Alu retroelements. Alu transcripts were induced by type I interferon and stimulated proinflammatory cytokine secretion by human peripheral blood cells. Ro60 deletion resulted in enhanced expression of Alu RNAs and interferon-regulated genes. Anti-Ro60-positive SLE immune complexes contained Alu RNAs, and Alu transcripts were up-regulated in SLE whole blood samples relative to controls. These findings establish a link among the lupus autoantigen Ro60, Alu retroelements, and type I interferon.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ribonucleoproteins / Autoantigens / Sjogren's Syndrome / Gene Expression Regulation / Alu Elements / RNA, Small Cytoplasmic / Lupus Erythematosus, Systemic Limits: Humans Language: En Journal: Science Year: 2015 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ribonucleoproteins / Autoantigens / Sjogren's Syndrome / Gene Expression Regulation / Alu Elements / RNA, Small Cytoplasmic / Lupus Erythematosus, Systemic Limits: Humans Language: En Journal: Science Year: 2015 Document type: Article