The Ro60 autoantigen binds endogenous retroelements and regulates inflammatory gene expression.

TitleThe Ro60 autoantigen binds endogenous retroelements and regulates inflammatory gene expression.
Publication TypeJournal Article
Year of Publication2015
AuthorsHung T, Pratt GA, Sundararaman B, Townsend MJ, Chaivorapol C, Bhangale T, Graham RR, Ortmann W, Criswell LA, Yeo GW, Behrens TW
JournalScience
Volume350
Issue6259
Pagination455-9
Date Published2015 Oct 23
ISSN1095-9203
KeywordsAlu Elements, Antigen-Antibody Complex, Autoantibodies, Autoantigens, Cell Line, Gene Expression Regulation, Humans, Inflammation, Interferon Type I, Lupus Erythematosus, Systemic, Ribonucleoproteins, RNA, RNA, Small Cytoplasmic, Sjogren's Syndrome, Transcription, Genetic
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.

DOI10.1126/science.aac7442
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/26382853?dopt=Abstract
Alternate JournalScience
PubMed ID26382853
PubMed Central IDPMC4691329
Grant ListHG004659 / HG / NHGRI NIH HHS / United States
HG007005 / HG / NHGRI NIH HHS / United States
NS075449 / NS / NINDS NIH HHS / United States
R01 GM084317 / GM / NIGMS NIH HHS / United States
R01 HG004659 / HG / NHGRI NIH HHS / United States
R01 NS075449 / NS / NINDS NIH HHS / United States
Track(s): 
Bioinformatics and Systems Biology