The schizophrenia risk gene MIR137 acts as a hippocampal gene network node orchestrating the expression of genes relevant to nervous system development and function.

TitleThe schizophrenia risk gene MIR137 acts as a hippocampal gene network node orchestrating the expression of genes relevant to nervous system development and function.
Publication TypeJournal Article
Year of Publication2017
AuteursLoohuis, NFMOlde, Kasri, NNadif, Glennon, JC, van Bokhoven, H, Hébert, SS, Kaplan, BB, Martens, GJM, Aschrafi, A
JournalProg Neuropsychopharmacol Biol Psychiatry
Volume73
Pagination109-118
Date Published2017 Feb 06
ISSN1878-4216
KeywordsAnimals, 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.

DOI10.1016/j.pnpbp.2016.02.009
Alternate JournalProg. Neuropsychopharmacol. Biol. Psychiatry
PubMed ID26925706
PubMed Central IDPMC5002268
Grant ListZ99 MH999999 / / Intramural NIH HHS / United States