Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Ataxin-1
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Ataxins
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Cell Line, Transformed
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Cerebellum / pathology
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Disease Models, Animal
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Gene Expression Regulation / genetics
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Glutamine / genetics
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Humans
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Mice
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Mice, Transgenic
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MicroRNAs / physiology*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Phenylalanine / genetics
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Purkinje Cells / drug effects
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Purkinje Cells / metabolism*
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RNA, Small Interfering / pharmacology
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Spinocerebellar Ataxias / genetics*
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Spinocerebellar Ataxias / pathology
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Time Factors
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Transfection
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Trinucleotide Repeat Expansion / genetics*
Substances
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ATXN1 protein, human
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Ataxin-1
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Ataxins
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Atxn1 protein, mouse
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MicroRNAs
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Nerve Tissue Proteins
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Nuclear Proteins
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RNA, Small Interfering
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enhanced green fluorescent protein
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Glutamine
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Green Fluorescent Proteins
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Phenylalanine