학술논문

The Ro60 autoantigen binds endogenous retroelements and regulates inflammatory gene expression
Document Type
article
Source
Science. 350(6259)
Subject
Biomedical and Clinical Sciences
Immunology
Genetics
Autoimmune Disease
Lupus
Aetiology
2.1 Biological and endogenous factors
Inflammatory and immune system
Alu Elements
Antigen-Antibody Complex
Autoantibodies
Autoantigens
Cell Line
Gene Expression Regulation
Humans
Inflammation
Interferon Type I
Lupus Erythematosus
Systemic
RNA
RNA
Small Cytoplasmic
Ribonucleoproteins
Sjogren's Syndrome
Transcription
Genetic
General Science & Technology
Language
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.