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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 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.

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Figure 1: miR-19, miR-101 and miR-130 regulate ATXN1 levels.
Figure 2: Purkinje cell expression of miR-19, miR-101 and miR-130.
Figure 3: Inhibition of miRNA-mediated post-transcriptional regulation of polyQ-expanded ATXN1 causes more severe cytotoxicity in HEK293T cells.


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We thank N. Ao, Y. Liu and A. Liang of the Baylor College of Medicine In Situ Hybridization core for technical assistance and V.N. Kim and members of the Zoghbi laboratory for helpful discussions and comments on the manuscript. This research was supported by US National Institutes of Health grants NS27699 and HD24064 to H.Y.Z. and NS22920 to H.T.O. H.Y.Z. is an investigator with the Howard Hughes Medical Institute.

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Y.L. and H.Y.Z. designed the experiments. Y.L. carried out the majority of the experiments, with the exception of those comparing SCA1[82Q]Tg/+ and SCA1[82Q]Tg/Tg mice in Supplementary Figure 1 (J.R.G. and R.C.S.) and the RNA in situ hybridization experiments in Figure 2 (C.T.). Data analyses and interpretation were conducted by Y.L., H.T.O. and H.Y.Z. Y.L. and H.Y.Z. wrote the paper.

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Correspondence to Huda Y Zoghbi.

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Lee, Y., Samaco, R., Gatchel, J. et al. miR-19, miR-101 and miR-130 co-regulate ATXN1 levels to potentially modulate SCA1 pathogenesis. Nat Neurosci 11, 1137–1139 (2008).

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