MIR137 variants identified in psychiatric patients affect synaptogenesis and neuronal transmission gene sets

• Published in: Molecular psychiatry 2015-04, Vol.20 (4), p.472-481
• Main Authors: Strazisar, M, Cammaerts, S, van der Ven, K, Forero, D A, Lenaerts, A-S, Nordin, A, Almeida-Souza, L, Genovese, G, Timmerman, V, Liekens, A, De Rijk, P, Adolfsson, R, Callaerts, P, Del-Favero, J
• Format: Article
• Language: English
• Subjects: 631/337/384/331; 692/420/2489/144; 692/699/476/1333; 692/699/476/1799; association analysis; Behavioral Sciences; Biological Psychology; Bipolar disorder; Brain research; Cell Line, Tumor; central nervous system; Deregulation; Etiology; Female; Gene expression; Gene Expression Profiling; Gene Frequency; Genes; Genetic aspects; Genetics; genome scan metaanalysis; Genomes; Genomics; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Health aspects; Humans; knockout mice; Male; Medicine; Medicine & Public Health; Mental disorders; Mental Disorders - genetics; Mental Disorders - pathology; Microarray Analysis; MicroRNA; microRNA expression; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Minisatellite Repeats - genetics; miR 137; miRNA; Models, Molecular; Nervous system; Neural circuitry; Neuroblastoma - pathology; Neurogenesis - genetics; Neurosciences; Oligonucleotide Array Sequence Analysis; original-article; Pharmacotherapy; Psychiatric patients; Psychiatry; Psychological aspects; Schizophrenia; Sequence analysis; stem cells; Sweden; Synapses; Synaptic Transmission - genetics; Synaptogenesis; Transfection; wide association
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/mp.2014.53

Sequence analysis of 13 microRNA (miRNA) genes expressed in the human brain and located in genomic regions associated with schizophrenia and/or bipolar disorder, in a northern Swedish patient/control population, resulted in the discovery of two functional variants in the MIR137 gene. On the basis of their location and the allele frequency differences between patients and controls, we explored the hypothesis that the discovered variants impact the expression of the mature miRNA and consequently influence global mRNA expression affecting normal brain functioning. Using neuronal-like SH-SY5Y cells, we demonstrated significantly reduced mature miR-137 levels in the cells expressing the variant miRNA gene. Subsequent transcriptome analysis showed that the reduction in miR-137 expression led to the deregulation of gene sets involved in synaptogenesis and neuronal transmission, all implicated in psychiatric disorders. Our functional findings add to the growing data, which implicate that miR-137 has an important role in the etiology of psychiatric disorders and emphasizes its involvement in nervous system development and proper synaptic function.