Brief Communication abstract
Nature Neuroscience 11, 1137 - 1139 (2008)
Published online: 31 August 2008 | doi:10.1038/nn.2183
miR-19, miR-101 and miR-130 co-regulate ATXN1 levels to potentially modulate SCA1 pathogenesis
Yoontae Lee1,4, Rodney C Samaco1, Jennifer R Gatchel2, Christina Thaller3, Harry T Orr5 & Huda Y Zoghbi1,2,3,4
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.
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
- Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
- Departments of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
- Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA.
- Institute of Human Genetics, Department of Biochemistry, Biophysics and Molecular Biology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Correspondence to: Huda Y Zoghbi1,2,3,4 e-mail: hzoghbi@bcm.tmc.edu
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