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

Sophia Cammaerts; Mojca Strazisar; Bart Smets; Sarah Weckhuysen; Annelie Nordin; Peter De Jonghe; Rolf Adolfsson; Peter De Rijk; Jurgen Del Favero

doi:10.1371/journal.pone.0144428

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

PLoS One. 2015 Dec 29;10(12):e0144428. doi: 10.1371/journal.pone.0144428. eCollection 2015.

Authors

Sophia Cammaerts^{1

2}, Mojca Strazisar^{1

2}, Bart Smets^{1

3}, Sarah Weckhuysen^{1

4}, Annelie Nordin⁵, Peter De Jonghe^{1

4

6}, Rolf Adolfsson⁵, Peter De Rijk^{1

2}, Jurgen Del Favero^{1

2

7}

Affiliations

¹ University of Antwerp, Antwerp, Belgium.
² Applied Molecular Genomics Unit, Department of Molecular Genetics, VIB, Antwerp, Belgium.
³ Centralized Service Facility, Department of Molecular Genetics, VIB, Antwerp, Belgium.
⁴ Neurogenetics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
⁵ Division of Psychiatry, Department of Clinical Sciences, Umeå University, Umeå, Sweden.
⁶ Antwerp University Hospital, Antwerp, Belgium.
⁷ Multiplicom N.V., Niel, Belgium.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Gene Expression Profiling
Genomics
Humans
Ion Channels / genetics*
MicroRNAs / genetics*
Mutation
Neurotransmitter Agents / genetics*
Organ Specificity
Schizophrenia / genetics*

Substances

Ion Channels
MIRN204 microRNA, human
MIRN618 microRNA, human
MicroRNAs
Neurotransmitter Agents

Grants and funding

This work was supported by Research Foundation- Flanders (G027410N to JDF, http://www.fwo.be/) and by the University Research Fund (UA-KP BOF/MS-2013 6264 to MS, https://www.uantwerpen.be/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. JDF is besides his tenure track position at the University of Antwerp also acting CTO of Multiplicom N.V. Both mandates are independent from each other and Multiplicom N.V. has no financial interest nor investment in the current study. Multiplicom N.V. provided support in the form of salaries for author JDF, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of this author are articulated in the ‘author contributions’ section.