The Ro60 autoantigen binds endogenous retroelements and regulates inflammatory gene expression.
T Hung,
G A Pratt,
B Sundararaman,
M J Townsend,
C Chaivorapol,
T Bhangale,
R R Graham,
W Ortmann,
L A Criswell,
G W Yeo,
T W Behrens
Science (New York, N.Y.)
· 2015
· Vol. 350
(6259)
· pp. 455-9
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.
Publication Types
["Journal Article", "Research Support, N.I.H., Extramural", "Research Support, Non-U.S. Gov't", "Research Support, U.S. Gov't, Non-P.H.S."]
Keywords
MeSH Terms
["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", "SS-A Antigen"]
Funding
R01 HG004659
NHGRI NIH HHS
(United States)
U54 HG007005
NHGRI NIH HHS
(United States)
R01 NS075449
NINDS NIH HHS
(United States)
HG004659
NHGRI NIH HHS
(United States)
NS075449
NINDS NIH HHS
(United States)
HG007005
NHGRI NIH HHS
(United States)
R01 GM084317
NIGMS NIH HHS
(United States)
Linked Datasets (5)
SLE lupus RNA-seq
Homo sapiens119 data files
| File | Type | Size |
|---|---|---|
| LIB10005_SAM8749887_L1_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10005_SAM8749887_L1_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10008_SAM8749890_L1_R1.fastq.gz | RNA-Seq | 3.6 GB |
| LIB10011_SAM8749893_L2_R1.fastq.gz | RNA-Seq | 3.6 GB |
| LIB10014_SAM8749896_L3_R1.fastq.gz | RNA-Seq | 3.9 GB |
| LIB10019_SAM8749901_L2_R1.fastq.gz | RNA-Seq | 3.2 GB |
| LIB10022_SAM8749904_L1_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10025_SAM8749907_L1_R1.fastq.gz | RNA-Seq | 3.0 GB |
| LIB10031_SAM8749913_L4_R1.fastq.gz | RNA-Seq | 3.2 GB |
| LIB10034_SAM8749916_L2_R1.fastq.gz | RNA-Seq | 3.8 GB |
| LIB10037_SAM8749919_L3_R1.fastq.gz | RNA-Seq | 3.6 GB |
| LIB10040_SAM8749922_L2_R1.fastq.gz | RNA-Seq | 3.7 GB |
| LIB10042_SAM8749924_L1_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10045_SAM8749927_L3_R1.fastq.gz | RNA-Seq | 3.5 GB |
| LIB10048_SAM8749930_L4_R1.fastq.gz | RNA-Seq | 3.2 GB |
| LIB10051_SAM8749933_L2_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10054_SAM8749936_L1_R1.fastq.gz | RNA-Seq | 3.0 GB |
| LIB10057_SAM8749939_L2_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10060_SAM8749942_L4_R1.fastq.gz | RNA-Seq | 3.8 GB |
| LIB10063_SAM8749945_L7_R1.fastq.gz | RNA-Seq | 3.2 GB |
| LIB10066_SAM8749948_L2_R1.fastq.gz | RNA-Seq | 3.6 GB |
| LIB10068_SAM8749950_L3_R1.fastq.gz | RNA-Seq | 3.7 GB |
| LIB10071_SAM8749953_L2_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10074_SAM8749956_L3_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10076_SAM8749958_L5_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10082_SAM8749964_L6_R1.fastq.gz | RNA-Seq | 3.3 GB |
| LIB10085_SAM8749967_L8_R1.fastq.gz | RNA-Seq | 3.1 GB |
| LIB10088_SAM8749970_L1_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10091_SAM8749973_L3_R1.fastq.gz | RNA-Seq | 3.3 GB |
| LIB10093_SAM8749975_L2_R1.fastq.gz | RNA-Seq | 3.1 GB |
| LIB10096_SAM8749978_L3_R1.fastq.gz | RNA-Seq | 3.6 GB |
| LIB10098_SAM8749980_L3_R1.fastq.gz | RNA-Seq | 3.0 GB |
| LIB10101_SAM8749983_L1_R1.fastq.gz | RNA-Seq | 3.3 GB |
| LIB10104_SAM8749986_L6_R1.fastq.gz | RNA-Seq | 3.3 GB |
| LIB10106_SAM8749988_L2_R1.fastq.gz | RNA-Seq | 3.1 GB |
| LIB10109_SAM8749991_L4_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10112_SAM8749994_L5_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10115_SAM8749997_L1_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10120_SAM8750002_L1_R1.fastq.gz | RNA-Seq | 2.9 GB |
| LIB10123_SAM8750005_L7_R1.fastq.gz | RNA-Seq | 3.3 GB |
| LIB10125_SAM8750007_L1_R1.fastq.gz | RNA-Seq | 3.2 GB |
| LIB10128_SAM8750010_L1_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10130_SAM8750012_L2_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10133_SAM8750015_L4_R1.fastq.gz | RNA-Seq | 3.7 GB |
| LIB10135_SAM8750017_L6_R1.fastq.gz | RNA-Seq | 2.7 GB |
| LIB10138_SAM8750020_L1_R1.fastq.gz | RNA-Seq | 3.3 GB |
| LIB10141_SAM8750023_L4_R1.fastq.gz | RNA-Seq | 3.5 GB |
| LIB10143_SAM8750025_L1_R1.fastq.gz | RNA-Seq | 3.1 GB |
| LIB10146_SAM8750028_L2_R1.fastq.gz | RNA-Seq | 3.6 GB |
| LIB10150_SAM8750032_L4_R1.fastq.gz | RNA-Seq | 3.1 GB |
| LIB10153_SAM8750035_L3_R1.fastq.gz | RNA-Seq | 3.1 GB |
| LIB10158_SAM8750040_L4_R1.fastq.gz | RNA-Seq | 3.1 GB |
| LIB10163_SAM8750045_L2_R1.fastq.gz | RNA-Seq | 3.7 GB |
| LIB10166_SAM8750048_L3_R1.fastq.gz | RNA-Seq | 3.8 GB |
| LIB10169_SAM8750051_L3_R1.fastq.gz | RNA-Seq | 3.3 GB |
| LIB10172_SAM8750054_L3_R1.fastq.gz | RNA-Seq | 3.0 GB |
| LIB10175_SAM8750057_L1_R1.fastq.gz | RNA-Seq | 3.7 GB |
| LIB10178_SAM8750060_L2_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10181_SAM8750063_L6_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10183_SAM8750065_L3_R1.fastq.gz | RNA-Seq | 4.2 GB |
| LIB10185_SAM8750067_L5_R1.fastq.gz | RNA-Seq | 2.9 GB |
| LIB10188_SAM8750070_L3_R1.fastq.gz | RNA-Seq | 2.8 GB |
| LIB10191_SAM8750073_L7_R1.fastq.gz | RNA-Seq | 3.1 GB |
| LIB10194_SAM8750076_L3_R1.fastq.gz | RNA-Seq | 3.5 GB |
| LIB10199_SAM8750081_L5_R1.fastq.gz | RNA-Seq | 3.3 GB |
| LIB10202_SAM8750084_L5_R1.fastq.gz | RNA-Seq | 2.8 GB |
| LIB10205_SAM8750087_L2_R1.fastq.gz | RNA-Seq | 3.5 GB |
| LIB10208_SAM8750090_L2_R1.fastq.gz | RNA-Seq | 3.6 GB |
| LIB10213_SAM8750095_L3_R1.fastq.gz | RNA-Seq | 3.7 GB |
| LIB10215_SAM8750097_L7_R1.fastq.gz | RNA-Seq | 3.3 GB |
| LIB10218_SAM8750100_L3_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10221_SAM8750103_L2_R1.fastq.gz | RNA-Seq | 3.6 GB |
| LIB10221_SAM8750103_L2_R1.fastq.gz | RNA-Seq | 3.6 GB |
| LIB10222_SAM8750104_L2_R1.fastq.gz | RNA-Seq | 3.8 GB |
| LIB10224_SAM8750106_L6_R1.fastq.gz | RNA-Seq | 3.8 GB |
| LIB10226_SAM8750108_L3_R1.fastq.gz | RNA-Seq | 3.6 GB |
| LIB10229_SAM8750111_L1_R1.fastq.gz | RNA-Seq | 2.9 GB |
| LIB10231_SAM8750113_L4_R1.fastq.gz | RNA-Seq | 3.3 GB |
| LIB10234_SAM8750116_L7_R1.fastq.gz | RNA-Seq | 3.0 GB |
| LIB10237_SAM8750119_L2_R1.fastq.gz | RNA-Seq | 3.3 GB |
| LIB10240_SAM8750122_L2_R1.fastq.gz | RNA-Seq | 3.6 GB |
| LIB10242_SAM8750124_L1_R1.fastq.gz | RNA-Seq | 3.0 GB |
| LIB10247_SAM8750129_L4_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10250_SAM8750132_L4_R1.fastq.gz | RNA-Seq | 3.0 GB |
| LIB10253_SAM8750135_L7_R1.fastq.gz | RNA-Seq | 3.8 GB |
| LIB10256_SAM8750138_L2_R1.fastq.gz | RNA-Seq | 3.0 GB |
| LIB10258_SAM8750140_L3_R1.fastq.gz | RNA-Seq | 3.2 GB |
| LIB10261_SAM8750143_L6_R1.fastq.gz | RNA-Seq | 2.7 GB |
| LIB10268_SAM8750150_L2_R1.fastq.gz | RNA-Seq | 3.3 GB |
| LIB10271_SAM8750153_L2_R1.fastq.gz | RNA-Seq | 3.9 GB |
| LIB10275_SAM8750157_L7_R1.fastq.gz | RNA-Seq | 3.2 GB |
| LIB10278_SAM8750160_L3_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10281_SAM8750163_L3_R1.fastq.gz | RNA-Seq | 4.2 GB |
| LIB10284_SAM8750166_L1_R1.fastq.gz | RNA-Seq | 3.3 GB |
| LIB10287_SAM8750169_L2_R1.fastq.gz | RNA-Seq | 2.9 GB |
| LIB10290_SAM8750172_L2_R1.fastq.gz | RNA-Seq | 4.0 GB |
| LIB10292_SAM8750174_L3_R1.fastq.gz | RNA-Seq | 3.8 GB |
| LIB10293_SAM8750175_L1_R1.fastq.gz | RNA-Seq | 3.2 GB |
| LIB10294_SAM8750176_L1_R1.fastq.gz | RNA-Seq | 3.2 GB |
| LIB10295_SAM8750177_L8_R1.fastq.gz | RNA-Seq | 2.9 GB |
| LIB10296_SAM8750178_L8_R1.fastq.gz | RNA-Seq | 2.7 GB |
| LIB10297_SAM8750179_L7_R1.fastq.gz | RNA-Seq | 3.5 GB |
| LIB10298_SAM8750180_L1_R1.fastq.gz | RNA-Seq | 4.2 GB |
| LIB10299_SAM8750181_L8_R1.fastq.gz | RNA-Seq | 2.8 GB |
| LIB10300_SAM8750182_L3_R1.fastq.gz | RNA-Seq | 3.5 GB |
| LIB10302_SAM8750184_L8_R1.fastq.gz | RNA-Seq | 6.1 GB |
| LIB10303_SAM8750185_L3_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10304_SAM8750186_L3_R1.fastq.gz | RNA-Seq | 3.3 GB |
| LIB10305_SAM8750187_L1_R1.fastq.gz | RNA-Seq | 3.1 GB |
| LIB10306_SAM8750188_L3_R1.fastq.gz | RNA-Seq | 3.1 GB |
| LIB10307_SAM8750189_L3_R1.fastq.gz | RNA-Seq | 4.0 GB |
| LIB10309_SAM8750191_L2_R1.fastq.gz | RNA-Seq | 3.1 GB |
| LIB10310_SAM8750192_L2_R1.fastq.gz | RNA-Seq | 3.4 GB |
| LIB10311_SAM8750193_L1_R1.fastq.gz | RNA-Seq | 2.8 GB |
| LIB10722_SAM9103789_L3_R1.fastq.gz | RNA-Seq | 3.6 GB |
| LIB10725_SAM9103792_L4_R1.fastq.gz | RNA-Seq | 3.6 GB |
| LIB10726_SAM9103793_L1_R1.fastq.gz | RNA-Seq | 2.8 GB |
| LIB11106_SAM9260118_L2_R1.fastq.gz | RNA-Seq | 2.9 GB |
| LIB11110_SAM9260122_L2_R1.fastq.gz | RNA-Seq | 2.8 GB |
Ro60-knockout cells
Homo sapiens10 data files
| File | Type | Size |
|---|---|---|
| LIB23499_SAM19353342_R1.fastq.gz | RNA-Seq | 1.0 GB |
| LIB23501_SAM19353346_R1.fastq.gz | RNA-Seq | 863.2 MB |
| LIB23503_SAM19353350_R1.fastq.gz | RNA-Seq | 1.1 GB |
| LIB23505_SAM19353354_R1.fastq.gz | RNA-Seq | 1.1 GB |
| LIB23506_SAM19353355_R1.fastq.gz | RNA-Seq | 1.0 GB |
| LIB24542_SAM19590764_R1.fastq.gz | RNA-Seq | 1.0 GB |
| LIB24543_SAM19590765_R1.fastq.gz | RNA-Seq | 1.1 GB |
| LIB24544_SAM19590766_R1.fastq.gz | RNA-Seq | 860.2 MB |
| LIB24545_SAM19590767_R1.fastq.gz | RNA-Seq | 968.6 MB |
| LIB24546_SAM19590768_R1.fastq.gz | RNA-Seq | 1007.7 MB |
Healthy donor PBMC RNA-seq with or without interferon-alpha stimulation
Homo sapiens6 data files
| File | Type | Size |
|---|---|---|
| LIB8209_SAM2707857_L1_R1.fastq.gz | RNA-Seq | 3.2 GB |
| LIB8210_SAM2707858_L1_R1.fastq.gz | RNA-Seq | 2.2 GB |
| LIB8212_SAM2707860_L1_R1.fastq.gz | RNA-Seq | 2.1 GB |
| LIB8213_SAM2707861_L1_R1.fastq.gz | RNA-Seq | 1.9 GB |
| LIB8215_SAM2707863_L1_R1.fastq.gz | RNA-Seq | 2.6 GB |
| LIB8566_SAM2707864_L5_R1.fastq.gz | RNA-Seq | 4.7 GB |
The Ro60 Autoantigen Binds Endogenous Retroelements and Regulates Inflammatory Gene Expression
Homo sapiensAnalysis Pipelines (5)
GSE72420 Data Processing
3 steps
geo_data_processing
GSE72420
GSE72500 iCLIP Data Processing
3 steps
GSE72501 Data Processing
5 steps
geo_data_processing
GSE72501
GSE72502 RNA-seq Data Processing
5 steps
GSE72509 RNA-seq Data Processing
5 steps