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RNA. 2014 Dec;20(12):1929-43. doi: 10.1261/rna.047225.114. Epub 2014 Oct 24.

Generation of a neuro-specific microarray reveals novel differentially expressed noncoding RNAs in mouse models for neurodegenerative diseases.

Author information

1
Division of Genomics and RNomics, Innsbruck Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria.
2
RNA Biology Group, Institute for Genomics and Bioinformatics, Graz University of Technology, 8010 Graz, Austria.
3
Department of Psychiatry and Psychotherapy, University Clinic of General and Social Psychiatry, Innsbruck Medical University, 6020 Innsbruck, Austria.
4
Division of Physiology, Department of Physiology and Medical Physics, Innsbruck Medical University, 6020 Innsbruck, Austria.
5
Pharmacology and Toxicology, Institute of Pharmacy, and Center for Molecular Biosciences, University of Innsbruck, 6020 Innsbruck, Austria.
6
Division of Genomics and RNomics, Innsbruck Biocenter, Medical University of Innsbruck, 6020 Innsbruck, Austria alexander.huettenhofer@i-med.ac.at.

Abstract

We have generated a novel, neuro-specific ncRNA microarray, covering 1472 ncRNA species, to investigate their expression in different mouse models for central nervous system diseases. Thereby, we analyzed ncRNA expression in two mouse models with impaired calcium channel activity, implicated in Epilepsy or Parkinson's disease, respectively, as well as in a mouse model mimicking pathophysiological aspects of Alzheimer's disease. We identified well over a hundred differentially expressed ncRNAs, either from known classes of ncRNAs, such as miRNAs or snoRNAs or which represented entirely novel ncRNA species. Several differentially expressed ncRNAs in the calcium channel mouse models were assigned as miRNAs and target genes involved in calcium signaling, thus suggesting feedback regulation of miRNAs by calcium signaling. In the Alzheimer mouse model, we identified two snoRNAs, whose expression was deregulated prior to amyloid plaque formation. Interestingly, the presence of snoRNAs could be detected in cerebral spine fluid samples in humans, thus potentially serving as early diagnostic markers for Alzheimer's disease. In addition to known ncRNAs species, we also identified 63 differentially expressed, entirely novel ncRNA candidates, located in intronic or intergenic regions of the mouse genome, genomic locations, which previously have been shown to harbor the majority of functional ncRNAs.

KEYWORDS:

Alzheimer's disease; Parkinson's disease; microarray; noncoding RNAs; snoRNA; voltage-gated Ca2+ channels

PMID:
25344396
PMCID:
PMC4238357
DOI:
10.1261/rna.047225.114
[Indexed for MEDLINE]
Free PMC Article

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