title: The Ro60 autoantigen binds endogenous retroelements and regulates inflammatory gene expression.
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.
authors.affiliation: Genentech, South San Francisco, CA 94080, USA. behrens.tim@gene.com hungt2@gene.com geneyeo@ucsd.edu.
authors.forename: T
authors.initials: T
authors.lastname: Hung
authors.affiliation: 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.
authors.forename: G A
authors.initials: GA
authors.lastname: Pratt
authors.affiliation: 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.
authors.forename: B
authors.initials: B
authors.lastname: Sundararaman
authors.affiliation: Genentech, South San Francisco, CA 94080, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Townsend
authors.affiliation: Genentech, South San Francisco, CA 94080, USA.
authors.forename: C
authors.initials: C
authors.lastname: Chaivorapol
authors.affiliation: Genentech, South San Francisco, CA 94080, USA.
authors.forename: T
authors.initials: T
authors.lastname: Bhangale
authors.affiliation: Genentech, South San Francisco, CA 94080, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Graham
authors.affiliation: Genentech, South San Francisco, CA 94080, USA.
authors.forename: W
authors.initials: W
authors.lastname: Ortmann
authors.affiliation: Rosalind Russell/Ephraim P. Engleman Rheumatology Research Center, University of California, San Francisco, CA 94143, USA.
authors.forename: L A
authors.initials: LA
authors.lastname: Criswell
authors.affiliation: 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, Singapore. Genome Institute of Singapore and Molecular Engineering Laboratory, Agency for Science, Technology and Research, Singapore. behrens.tim@gene.com hungt2@gene.com geneyeo@ucsd.edu.
authors.forename: G W
authors.initials: GW
authors.lastname: Yeo
authors.affiliation: Genentech, South San Francisco, CA 94080, USA. behrens.tim@gene.com hungt2@gene.com geneyeo@ucsd.edu.
authors.forename: T W
authors.initials: TW
authors.lastname: Behrens
mesh_terms: D020087:Alu Elements; D000936:Antigen-Antibody Complex / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics; D007370:Interferon Type I; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D012313:RNA / Q000378:metabolism; D020733:RNA, Small Cytoplasmic / Q000276:immunology / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000276:immunology / Q000378:metabolism*; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000276:immunology; D014158:Transcription, Genetic; D000099207:SS-A Antigen
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001324:Autoantigens; D007370:Interferon Type I; D012313:RNA; D020733:RNA, Small Cytoplasmic; D012261:Ribonucleoproteins; C116006:RO60 protein, human; D000099207:SS-A Antigen