1. A novel long non-coding RNA in the rheumatoid arthritis risk locus TRAF1-C5 influences C5 mRNA levels.
- Author
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Messemaker TC, Frank-Bertoncelj M, Marques RB, Adriaans A, Bakker AM, Daha N, Gay S, Huizinga TW, Toes RE, Mikkers HM, and Kurreeman F
- Subjects
- Alpha-Amanitin pharmacology, Arthritis, Rheumatoid metabolism, Arthritis, Rheumatoid pathology, Cell Line, Tumor, DNA, Intergenic metabolism, Fibroblasts cytology, Fibroblasts drug effects, Genetic Loci, Genotype, Hepatocytes cytology, Hepatocytes drug effects, Hepatocytes metabolism, Humans, Monocytes cytology, Monocytes drug effects, Monocytes metabolism, Nucleic Acid Synthesis Inhibitors pharmacology, Polymorphism, Single Nucleotide, Primary Cell Culture, RNA, Long Noncoding antagonists & inhibitors, RNA, Long Noncoding metabolism, RNA, Messenger antagonists & inhibitors, RNA, Messenger metabolism, RNA, Small Interfering genetics, RNA, Small Interfering metabolism, Synovial Membrane cytology, Synovial Membrane drug effects, Synovial Membrane metabolism, Transcription, Genetic drug effects, Arthritis, Rheumatoid genetics, DNA, Intergenic genetics, Fibroblasts metabolism, Genetic Predisposition to Disease, RNA, Long Noncoding genetics, RNA, Messenger genetics
- Abstract
Long non-coding RNAs (lncRNAs) can regulate the transcript levels of genes in the same genomic region. These locally acting lncRNAs have been found deregulated in human disease and some have been shown to harbour quantitative trait loci (eQTLs) in autoimmune diseases. However, lncRNAs linked to the transcription of candidate risk genes in loci associated to rheumatoid arthritis (RA) have not yet been identified. The TRAF1 and C5 risk locus shows evidence of multiple eQTLs and transcription of intergenic non-coding sequences. Here, we identified a non-coding transcript (C5T1lncRNA) starting in the 3' untranslated region (UTR) of C5. RA-relevant cell types express C5T1lncRNA and RNA levels are further enhanced by specific immune stimuli. C5T1lncRNA is expressed predominantly in the nucleus and its expression correlates positively with C5 mRNA in various tissues (P=0.001) and in peripheral blood mononuclear cells (P=0.02) indicating transcriptional co-regulation. Knockdown results in a concurrent decrease in C5 mRNA levels but not of other neighbouring genes. Overall, our data show the identification of a novel lncRNA C5T1lncRNA that is fully located in the associated region and influences transcript levels of C5, a gene previously linked to RA pathogenesis.
- Published
- 2016
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