Upregulation of a small vault RNA (svtRNA2-1a) is an early event in parkinson disease and induces neuronal dysfunction

Elena Minones-Moyano, Marc R. Friedländer, Joan Pallares, Birgit Kagerbauer, Silvia Porta, Georgia Escaramis, Isidre Ferrer, Xavier P. Estivill, Eulalia Marti

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) and other small non-coding RNAs (sncRNAs) are post-transcriptional regulators of gene expression, playing key roles in neuronal development, plasticity and disease. Transcriptome deregulation caused by miRNA dysfunction has been associated to neurodegenerative diseases. Parkinson disease (PD) is the second most common neurodegenerative disease showing deregulation of the coding and small non-coding transcriptome. On profiling sncRNA in PD brain areas differently affected, we found that upregulation of a small vault RNA (svtRNA2-1a) is widespread in PD brains, occurring early in the course of the disease (at pre-motor stages). SvtRNA2-1a biogenesis was dependent on Dicer activity on its precursor (vtRNA2-1) but independent of Drosha endonuclease, unlike the canonical miRNAs. Although endogenous svtRNA2-1a was enriched in Ago-2 immunoprecipitates in differentiated SH -SY5Y neuronal cells, overexpression of svtRNA2-1a induced subtle transcriptomic changes, suggesting that gene expression regulation may involve other mechanisms than mRNA decay only. Function enrichment analysis of the genes deregulated by svtRNA2-1a overexpression or svtRNA2-1a predicted targets identified pathways related to nervous system development and cell type specification. The expression pattern of svtRNA2-1a during development and aging of the human brain and the detrimental consequences of a svtRNA2-1a mimic overexpression in neuronal cells further indicate that low svtRNA2-1a levels may be important for the maintenance of neurons. Our results suggest that early svtRNA2-1a upregulation in PD may contribute to perturbations of gene expression networks, underlying metabolic impairment and cell dysfunction. A better understanding of the pathways regulated by svtRNA2-A, and also the mechanisms regulating its expression should facilitate the identification of new targets for therapeutic approaches in PD.

Original languageEnglish
Pages (from-to)1093-1106
Number of pages14
JournalRNA Biology
Volume10
Issue number7
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Parkinson Disease
Up-Regulation
RNA
MicroRNAs
Small Untranslated RNA
Transcriptome
Neurodegenerative Diseases
Brain
Gene Expression
Neuronal Plasticity
Gene Regulatory Networks
Endonucleases
RNA Stability
Gene Expression Regulation
Human Development
Regulator Genes
Nervous System
Maintenance
Neurons
Genes

Keywords

  • Lincrnas
  • Microarrays
  • Neuronal dysfunction
  • Parkinson disease
  • SncRNA
  • Vault RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Minones-Moyano, E., Friedländer, M. R., Pallares, J., Kagerbauer, B., Porta, S., Escaramis, G., ... Marti, E. (2013). Upregulation of a small vault RNA (svtRNA2-1a) is an early event in parkinson disease and induces neuronal dysfunction. RNA Biology, 10(7), 1093-1106. https://doi.org/10.4161/rna.24813

Upregulation of a small vault RNA (svtRNA2-1a) is an early event in parkinson disease and induces neuronal dysfunction. / Minones-Moyano, Elena; Friedländer, Marc R.; Pallares, Joan; Kagerbauer, Birgit; Porta, Silvia; Escaramis, Georgia; Ferrer, Isidre; Estivill, Xavier P.; Marti, Eulalia.

In: RNA Biology, Vol. 10, No. 7, 2013, p. 1093-1106.

Research output: Contribution to journalArticle

Minones-Moyano, E, Friedländer, MR, Pallares, J, Kagerbauer, B, Porta, S, Escaramis, G, Ferrer, I, Estivill, XP & Marti, E 2013, 'Upregulation of a small vault RNA (svtRNA2-1a) is an early event in parkinson disease and induces neuronal dysfunction', RNA Biology, vol. 10, no. 7, pp. 1093-1106. https://doi.org/10.4161/rna.24813
Minones-Moyano E, Friedländer MR, Pallares J, Kagerbauer B, Porta S, Escaramis G et al. Upregulation of a small vault RNA (svtRNA2-1a) is an early event in parkinson disease and induces neuronal dysfunction. RNA Biology. 2013;10(7):1093-1106. https://doi.org/10.4161/rna.24813
Minones-Moyano, Elena ; Friedländer, Marc R. ; Pallares, Joan ; Kagerbauer, Birgit ; Porta, Silvia ; Escaramis, Georgia ; Ferrer, Isidre ; Estivill, Xavier P. ; Marti, Eulalia. / Upregulation of a small vault RNA (svtRNA2-1a) is an early event in parkinson disease and induces neuronal dysfunction. In: RNA Biology. 2013 ; Vol. 10, No. 7. pp. 1093-1106.
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