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Journal of Nucleic Acids
Volume 2012 (2012), Article ID 672536, 11 pages
Research Article

Functional Annotation of Small Noncoding RNAs Target Genes Provides Evidence for a Deregulated Ubiquitin-Proteasome Pathway in Spinocerebellar Ataxia Type 1

1Department of Medical Genetics, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands
2Animal Science Department, Biomedical Primate Research Centre, Lange Kleiweg 139, 2288 GJ Rijswijk, The Netherlands
3Department of Comparative Genetics and Refinement, Biomedical Primate Research Center, Lange Kleiweg 139, 2288 GJ Rijswijk, The Netherlands

Received 14 May 2012; Accepted 30 July 2012

Academic Editor: Kenneth K. W. To

Copyright © 2012 Stephan Persengiev et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder caused by the expansion of CAG repeats in the ataxin 1 (ATXN1) gene. In affected cerebellar neurons of patients, mutant ATXN1 accumulates in ubiquitin-positive nuclear inclusions, indicating that protein misfolding is involved in SCA1 pathogenesis. In this study, we functionally annotated the target genes of the small noncoding RNAs (ncRNAs) that were selectively activated in the affected brain compartments. The primary targets of these RNAs, which exhibited a significant enrichment in the cerebellum and cortex of SCA1 patients, were members of the ubiquitin-proteasome system. Thus, we identified and functionally annotated a plausible regulatory pathway that may serve as a potential target to modulate the outcome of neurodegenerative diseases.