title: Novel brain expressed RNA identified at the MIR137 schizophrenia-associated locus.
abstract: Genome-wide association studies (GWAS) have identified a locus on chromosome 1p21.3 to be highly associated with schizophrenia. A microRNA, MIR137, within this locus has been proposed as the gene causally associated with schizophrenia, due to its known role as a regulator of neuronal development and function. However, the involvement of other genes within this region, including DPYD (dihydropyrimidine dehydrogenase), is also plausible. In this communication, we describe a previously uncharacterised, brain-expressed RNA, EU358092, within the schizophrenia-associated region at 1p21.3. As we observed for MIR137, EU358092 expression was modulated in response to psychoactive drug treatment in the human SH-SY5Y neuroblastoma cell line. Bioinformatic analysis of publically available CNS expression data indicates that MIR137 and EU358092 are often co-expressed in vivo. A potential regulatory domain for expression of EU358092 is identified by bioinformatic analysis and its regulatory function is confirmed by reporter gene assays. These data suggest a potentially important role for EU358092 in the aetiology of schizophrenia, either individually or in combination with other genes at this locus.
authors.affiliation: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, The University of Liverpool, Liverpool L69 3BX, UK.
authors.forename: Olympia
authors.initials: O
authors.lastname: Gianfrancesco
authors.affiliation: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, The University of Liverpool, Liverpool L69 3BX, UK.
authors.forename: Alix
authors.initials: A
authors.lastname: Warburton
authors.affiliation: Eli Lilly and Company Limited, Windlesham, Surrey, UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Collier
authors.affiliation: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, The University of Liverpool, Liverpool L69 3BX, UK.
authors.forename: Vivien J
authors.initials: VJ
authors.lastname: Bubb
authors.affiliation: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, The University of Liverpool, Liverpool L69 3BX, UK. Electronic address: jquinn@liverpool.ac.uk.
authors.forename: John P
authors.initials: JP
authors.lastname: Quinn
mesh_terms: D001921:Brain / Q000378:metabolism*; D045744:Cell Line, Tumor; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics*; D056426:Genetic Loci; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
chemical_list: C545567:MIRN137 microRNA, human; D035683:MicroRNAs
keywords: EU358092; Schizophrenia; lncRNA; microRNA-137