Nature Communications (Jul 2017)
SRSF1-dependent nuclear export inhibition of C9ORF72 repeat transcripts prevents neurodegeneration and associated motor deficits
- Guillaume M. Hautbergue,
- Lydia M. Castelli,
- Laura Ferraiuolo,
- Alvaro Sanchez-Martinez,
- Johnathan Cooper-Knock,
- Adrian Higginbottom,
- Ya-Hui Lin,
- Claudia S. Bauer,
- Jennifer E. Dodd,
- Monika A. Myszczynska,
- Sarah M. Alam,
- Pierre Garneret,
- Jayanth S. Chandran,
- Evangelia Karyka,
- Matthew J. Stopford,
- Emma F. Smith,
- Janine Kirby,
- Kathrin Meyer,
- Brian K. Kaspar,
- Adrian M. Isaacs,
- Sherif F. El-Khamisy,
- Kurt J. De Vos,
- Ke Ning,
- Mimoun Azzouz,
- Alexander J. Whitworth,
- Pamela J. Shaw
Affiliations
- Guillaume M. Hautbergue
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Lydia M. Castelli
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Laura Ferraiuolo
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Alvaro Sanchez-Martinez
- MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus
- Johnathan Cooper-Knock
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Adrian Higginbottom
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Ya-Hui Lin
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Claudia S. Bauer
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Jennifer E. Dodd
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Monika A. Myszczynska
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Sarah M. Alam
- MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus
- Pierre Garneret
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Jayanth S. Chandran
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Evangelia Karyka
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Matthew J. Stopford
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Emma F. Smith
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Janine Kirby
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Kathrin Meyer
- Department of Pediatrics, Nationwide Children’s Research Institute, The Ohio State University
- Brian K. Kaspar
- Department of Pediatrics, Nationwide Children’s Research Institute, The Ohio State University
- Adrian M. Isaacs
- Department of Neurodegenerative Disease, UCL Institute of Neurology
- Sherif F. El-Khamisy
- Department of Molecular Biology and Biotechnology, Krebs Institute, University of Sheffield
- Kurt J. De Vos
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Ke Ning
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Mimoun Azzouz
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- Alexander J. Whitworth
- MRC Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus
- Pamela J. Shaw
- Department of Neuroscience, Sheffield Institute for Translational Neuroscience, University of Sheffield
- DOI
- https://doi.org/10.1038/ncomms16063
- Journal volume & issue
-
Vol. 8,
no. 1
pp. 1 – 18
Abstract
The RNA for ALS- and frontotemporal dementia-associated C9ORF72 gene is exported from nucleus via an unknown mechanism. This study shows that reduction of nuclear export adaptor SRSF1 can alleviate neuronal cell death and nuclear export of C9ORF72 inDrosophilaand patient-derived induced motor neurons.
