miR-19, miR-101 and miR-130 co-regulate ATXN1 levels to potentially modulate SCA1 pathogenesis

Spinocerebellar ataxia type 1 is caused by expansion of a translated CAG repeat in ataxin1 (ATXN1). The level of the polyglutamine-expanded protein is one of the factors that contributes to disease severity. Here we found that miR-19, miR-101 and miR-130 co-regulate ataxin1 levels and that their inh...

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Veröffentlicht in:	Nature neuroscience 2008-10, Vol.11 (10), p.1137-1139
Hauptverfasser:	Gatchel, Jennifer R, Lee, Yoontae, Thaller, Christina, Zoghbi, Huda Y, Orr, Harry T, Samaco, Rodney C
Format:	Artikel
Sprache:	eng
Schlagworte:	Animal Genetics and Genomics Animals Ataxia Ataxin-1 Ataxins Behavioral Sciences Binding sites Biological Techniques Biomedical and Life Sciences Biomedicine brief-communication Cell Line, Transformed Cellular proteins Cerebellum - pathology Degeneration Disease Disease Models, Animal Gene expression Gene Expression Regulation - genetics Genetic aspects Glutamine - genetics Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism Humans Mice Mice, Transgenic MicroRNAs MicroRNAs - physiology Molecular biology Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Nervous system Neurobiology Neurosciences Nuclear Proteins - genetics Nuclear Proteins - metabolism Pathogenesis Phenylalanine - genetics Proteins Purkinje Cells - drug effects Purkinje Cells - metabolism RNA, Small Interfering - pharmacology Spinocerebellar Ataxias - genetics Spinocerebellar Ataxias - pathology Time Factors Transfection Trinucleotide Repeat Expansion - genetics
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Zusammenfassung:	Spinocerebellar ataxia type 1 is caused by expansion of a translated CAG repeat in ataxin1 (ATXN1). The level of the polyglutamine-expanded protein is one of the factors that contributes to disease severity. Here we found that miR-19, miR-101 and miR-130 co-regulate ataxin1 levels and that their inhibition enhanced the cytotoxicity of polyglutamine-expanded ATXN1 in human cells. We provide a new candidate mechanism for modulating the pathogenesis of neurodegenerative diseases sensitive to protein dosage.
ISSN:	1097-6256 1546-1726
DOI:	10.1038/nn.2183