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