A novel long non-coding RNA in the rheumatoid arthritis risk locus TRAF1-C5 influences C5 mRNA levels

• Published in: Genes and immunity Vol. 17; no. 2; pp. 85 - 92
• Main Authors: Messemaker, T C, Frank-Bertoncelj, M, Marques, R B, Adriaans, A, Bakker, A M, Daha, N, Gay, S, Huizinga, T W, Toes, R E M, Mikkers, H M M, Kurreeman, F
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.03.2016
• Subjects: 3' Untranslated regions; Alpha-Amanitin - pharmacology; Analysis; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - metabolism; Arthritis, Rheumatoid - pathology; Autoimmune diseases; Care and treatment; Cell Line, Tumor; Complications and side effects; Development and progression; DNA, Intergenic - genetics; DNA, Intergenic - metabolism; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Gene regulation; Genetic aspects; Genetic Loci; Genetic Predisposition to Disease; Genetic research; Genetic transcription; Genotype; Health aspects; Hepatocytes - cytology; Hepatocytes - drug effects; Hepatocytes - metabolism; Humans; Identification and classification; Influence; Leukocytes (mononuclear); Messenger RNA; Monocytes - cytology; Monocytes - drug effects; Monocytes - metabolism; Non-coding RNA; Nucleic Acid Synthesis Inhibitors - pharmacology; Peripheral blood mononuclear cells; Polymorphism, Single Nucleotide; Primary Cell Culture; Quantitative genetics; Quantitative trait loci; Rheumatoid arthritis; Risk factors; RNA; RNA, Long Noncoding - antagonists & inhibitors; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; RNA, Messenger - antagonists & inhibitors; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; Synovial Membrane - cytology; Synovial Membrane - drug effects; Synovial Membrane - metabolism; Transcription; Transcription, Genetic - drug effects; Netherlands
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/gene.2015.54

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.