title: MIR137 variants identified in psychiatric patients affect synaptogenesis and neuronal transmission gene sets.
abstract: 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.
authors.affiliation: 1] Applied Molecular Genomics Unit, Department of Molecular Genetics, VIB, Antwerp, Belgium [2] University of Antwerp, Antwerp, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Strazisar
authors.affiliation: 1] Applied Molecular Genomics Unit, Department of Molecular Genetics, VIB, Antwerp, Belgium [2] University of Antwerp, Antwerp, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Cammaerts
authors.affiliation: 1] Applied Molecular Genomics Unit, Department of Molecular Genetics, VIB, Antwerp, Belgium [2] University of Antwerp, Antwerp, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: van der Ven
authors.affiliation: 1] Applied Molecular Genomics Unit, Department of Molecular Genetics, VIB, Antwerp, Belgium [2] University of Antwerp, Antwerp, Belgium [3] Biomedical Sciences Research Group, School of Medicine, Universidad Antonio Nariño, Bogotá, Colombia.
authors.forename: D A
authors.initials: DA
authors.lastname: Forero
authors.affiliation: 1] Applied Molecular Genomics Unit, Department of Molecular Genetics, VIB, Antwerp, Belgium [2] University of Antwerp, Antwerp, Belgium.
authors.forename: A-S
authors.initials: AS
authors.lastname: Lenaerts
authors.affiliation: Department of Clinical Sciences, Division of Psychiatry, Umeå University, Umeå, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Nordin
authors.affiliation: 1] University of Antwerp, Antwerp, Belgium [2] Peripheral Neuropathy Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Almeida-Souza
authors.affiliation: 1] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA [2] Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA [3] Department of Genetics, Harvard Medical School, Boston, MA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Genovese
authors.affiliation: 1] University of Antwerp, Antwerp, Belgium [2] Peripheral Neuropathy Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
authors.forename: V
authors.initials: V
authors.lastname: Timmerman
authors.affiliation: 1] Applied Molecular Genomics Unit, Department of Molecular Genetics, VIB, Antwerp, Belgium [2] University of Antwerp, Antwerp, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Liekens
authors.affiliation: 1] Applied Molecular Genomics Unit, Department of Molecular Genetics, VIB, Antwerp, Belgium [2] University of Antwerp, Antwerp, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: De Rijk
authors.affiliation: Department of Clinical Sciences, Division of Psychiatry, Umeå University, Umeå, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Adolfsson
authors.affiliation: VIB Laboratory of Behavioral and Developmental Genetics, KU Leuven, Leuven, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Callaerts
authors.affiliation: 1] Applied Molecular Genomics Unit, Department of Molecular Genetics, VIB, Antwerp, Belgium [2] University of Antwerp, Antwerp, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Del-Favero
mesh_terms: D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D005787:Gene Frequency; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D046228:Microarray Analysis; D018598:Minisatellite Repeats / Q000235:genetics*; D008958:Models, Molecular; D009447:Neuroblastoma / Q000473:pathology; D055495:Neurogenesis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D013548:Sweden; D009435:Synaptic Transmission / Q000235:genetics*; D014162:Transfection
chemical_list: D035683:MicroRNAs; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins