Schizophrenia-Associated MIR204 Regulates Noncoding RNAs and Affects Neurotransmitter and Ion Channel Gene Sets

As regulators of gene expression, microRNAs (miRNAs) are likely to play an important role in the development of disease. In this study we present a large-scale strategy to identify miRNAs with a role in the regulation of neuronal processes. Thereby we found variant rs7861254 located near the MIR204...

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Bibliographic Details
Published in:PloS one 2015-12, Vol.10 (12), p.e0144428-e0144428
Main Authors: Cammaerts, Sophia, Strazisar, Mojca, Smets, Bart, Weckhuysen, Sarah, Nordin, Annelie, De Jonghe, Peter, Adolfsson, Rolf, De Rijk, Peter, Del Favero, Jurgen
Format: Article
Language:English
Subjects:
Aging
Analysis
Cell Line, Tumor
Development and progression
Disease
Gene expression
Gene Expression Profiling
Genes
Genetic aspects
Genetics
Genomes
Genomics
Humans
Ion channels
Ion Channels - genetics
Medical research
Mental disorders
MicroRNA
MicroRNAs - genetics
miRNA
Mode of action
Mutation
Neurophysiology
Neuropsychology
Neurotransmitter Agents - genetics
Ontology
Organ Specificity
Patients
Psychiatry
Regulators
Schizophrenia
Schizophrenia - genetics
Studies
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Summary:As regulators of gene expression, microRNAs (miRNAs) are likely to play an important role in the development of disease. In this study we present a large-scale strategy to identify miRNAs with a role in the regulation of neuronal processes. Thereby we found variant rs7861254 located near the MIR204 gene to be significantly associated with schizophrenia. This variant resulted in reduced expression of miR-204 in neuronal-like SH-SY5Y cells. Analysis of the consequences of the altered miR-204 expression on the transcriptome of these cells uncovered a new mode of action for miR-204, being the regulation of noncoding RNAs (ncRNAs), including several miRNAs, such as MIR296. Furthermore, pathway analysis showed downstream effects of miR-204 on neurotransmitter and ion channel related gene sets, potentially mediated by miRNAs regulated through miR-204.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0144428