title: A novel long non-coding RNA in the rheumatoid arthritis risk locus TRAF1-C5 influences C5 mRNA levels.
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.
authors.affiliation: Department of Rheumatology, Leiden University Medical Centre, RC Leiden, The Netherlands.|Department of Molecular Cell Biology, Leiden University Medical Centre, RC Leiden, The Netherlands.
authors.forename: T C
authors.initials: TC
authors.lastname: Messemaker
authors.affiliation: Department of Rheumatology, Center of Experimental Rheumatology, University Hospital Zurich and University of Zurich, Schlieren, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Frank-Bertoncelj
authors.affiliation: Department of Rheumatology, Leiden University Medical Centre, RC Leiden, The Netherlands.
authors.forename: R B
authors.initials: RB
authors.lastname: Marques
authors.affiliation: Department of Rheumatology, Leiden University Medical Centre, RC Leiden, The Netherlands.|Department of Molecular Cell Biology, Leiden University Medical Centre, RC Leiden, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Adriaans
authors.affiliation: Department of Rheumatology, Leiden University Medical Centre, RC Leiden, The Netherlands.
authors.forename: A M
authors.initials: AM
authors.lastname: Bakker
authors.affiliation: Department of Rheumatology, Leiden University Medical Centre, RC Leiden, The Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: Daha
authors.affiliation: Department of Rheumatology, Center of Experimental Rheumatology, University Hospital Zurich and University of Zurich, Schlieren, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Gay
authors.affiliation: Department of Rheumatology, Leiden University Medical Centre, RC Leiden, The Netherlands.
authors.forename: T W
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Department of Rheumatology, Leiden University Medical Centre, RC Leiden, The Netherlands.
authors.forename: R E M
authors.initials: RE
authors.lastname: Toes
authors.affiliation: Department of Molecular Cell Biology, Leiden University Medical Centre, RC Leiden, The Netherlands.
authors.forename: H M M
authors.initials: HM
authors.lastname: Mikkers
authors.affiliation: Department of Rheumatology, Leiden University Medical Centre, RC Leiden, The Netherlands.|Department of Human Genetics, Leiden University Medical Centre, RC Leiden, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Kurreeman
mesh_terms: D053959:Alpha-Amanitin / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D021901:DNA, Intergenic / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D061251:Primary Cell Culture; D062085:RNA, Long Noncoding / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D053959:Alpha-Amanitin; D021901:DNA, Intergenic; D019384:Nucleic Acid Synthesis Inhibitors; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D034741:RNA, Small Interfering