Title | The schizophrenia risk gene MIR137 acts as a hippocampal gene network node orchestrating the expression of genes relevant to nervous system development and function. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Loohuis, NFMOlde, Kasri, NNadif, Glennon, JC, van Bokhoven, H, Hébert, SS, Kaplan, BB, Martens, GJM, Aschrafi, A |
Journal | Prog Neuropsychopharmacol Biol Psychiatry |
Volume | 73 |
Pagination | 109-118 |
Date Published | 2017 Feb 06 |
ISSN | 1878-4216 |
Keywords | Animals, Cells, Cultured, Embryo, Mammalian, Gene Expression Regulation, Developmental, Gene Ontology, Gene Regulatory Networks, HEK293 Cells, Hippocampus, Humans, MicroRNAs, Nervous System, Neurons, Rats, Rats, Wistar, RNA, Messenger, Schizophrenia, Transfection |
Abstract | MicroRNAs (miRs) are small regulatory molecules, which orchestrate neuronal development and plasticity through modulation of complex gene networks. MicroRNA-137 (miR-137) is a brain-enriched RNA with a critical role in regulating brain development and in mediating synaptic plasticity. Importantly, mutations in this miR are associated with the pathoetiology of schizophrenia (SZ), and there is a widespread assumption that disruptions in miR-137 expression lead to aberrant expression of gene regulatory networks associated with SZ. To systematically identify the mRNA targets for this miR, we performed miR-137 gain- and loss-of-function experiments in primary rat hippocampal neurons and profiled differentially expressed mRNAs through next-generation sequencing. We identified 500 genes that were bidirectionally activated or repressed in their expression by the modulation of miR-137 levels. Gene ontology analysis using two independent software resources suggested functions for these miR-137-regulated genes in neurodevelopmental processes, neuronal maturation processes and cell maintenance, all of which known to be critical for proper brain circuitry formation. Since many of the putative miR-137 targets identified here also have been previously shown to be associated with SZ, we propose that this miR acts as a critical gene network hub contributing to the pathophysiology of this neurodevelopmental disorder. |
DOI | 10.1016/j.pnpbp.2016.02.009 |
Alternate Journal | Prog. Neuropsychopharmacol. Biol. Psychiatry |
PubMed ID | 26925706 |
PubMed Central ID | PMC5002268 |
Grant List | Z99 MH999999 / / Intramural NIH HHS / United States |