miR-19, miR-101 and miR-130 co-regulate ATXN1 levels to potentially modulate SCA1 pathogenesis (original) (raw)
- Brief Communication
- Published: 31 August 2008
- Rodney C Samaco1,
- Jennifer R Gatchel2,
- Christina Thaller3,
- Harry T Orr5 &
- …
- Huda Y Zoghbi1,2,3,4
Nature Neuroscience volume 11, pages 1137–1139 (2008)Cite this article
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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.
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References
- Orr, H.T. & Zoghbi, H.Y. Annu. Rev. Neurosci. 30, 575–621 (2007).
Article CAS Google Scholar - Orr, H.T. et al. Nat. Genet. 4, 221–226 (1993).
Article CAS Google Scholar - Banfi, S. et al. Nat. Genet. 7, 513–520 (1994).
Article CAS Google Scholar - Burright, E.N. et al. Cell 82, 937–948 (1995).
Article CAS Google Scholar - Cemal, C.K. et al. Hum. Mol. Genet. 11, 1075–1094 (2002).
Article CAS Google Scholar - Xia, H. et al. Nat. Med. 10, 816–820 (2004).
Article CAS Google Scholar - Huynh, D.P., Figueroa, K., Hoang, N. & Pulst, S.M. Nat. Genet. 26, 44–50 (2000).
Article CAS Google Scholar - Bartel, D.P. Cell 116, 281–297 (2004).
Article CAS Google Scholar - Lewis, B.P., Shih, I.H., Jones-Rhoades, M.W., Bartel, D.P. & Burge, C.B. Cell 115, 787–798 (2003).
Article CAS Google Scholar - Krek, A. et al. Nat. Genet. 37, 495–500 (2005).
Article CAS Google Scholar - Schaefer, A. et al. J. Exp. Med. 204, 1553–1558 (2007).
Article CAS Google Scholar - Zoghbi, H.Y. & Orr, H.T. Semin. Cell Biol. 6, 29–35 (1995).
Article CAS Google Scholar - Clark, H.B. et al. J. Neurosci. 17, 7385–7395 (1997).
Article CAS Google Scholar - Rich, T. & Varadaraj, A. PLoS ONE 2, e1014 (2007).
Article Google Scholar - Lim, J. et al. Nature 452, 713–718 (2008).
Article CAS Google Scholar
Acknowledgements
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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Authors and Affiliations
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, 77030, Texas, USA
Yoontae Lee, Rodney C Samaco & Huda Y Zoghbi - Department of Neuroscience, Baylor College of Medicine, Houston, 77030, Texas, USA
Jennifer R Gatchel & Huda Y Zoghbi - Departments of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, 77030, Texas, USA
Christina Thaller & Huda Y Zoghbi - Howard Hughes Medical Institute, Baylor College of Medicine, Houston, 77030, Texas, USA
Yoontae Lee & Huda Y Zoghbi - Department of Biochemistry, Department of Laboratory Medicine and Pathology, Institute of Human Genetics, Biophysics and Molecular Biology, University of Minnesota, Minneapolis, 55455, Minnesota, USA
Harry T Orr
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Contributions
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 toHuda 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). https://doi.org/10.1038/nn.2183
- Received: 19 May 2008
- Accepted: 08 July 2008
- Published: 31 August 2008
- Issue Date: October 2008
- DOI: https://doi.org/10.1038/nn.2183