GGGGCC microsatellite RNA is neuritically localized, induces branching defects, and perturbs transport granule function
AuthorsBurguete, Alondra Schweizer
Akins, Michael R.
Bonini, Nancy M.
UMass Chan AffiliationsDepartment of Neurology
Molecular and Cellular Neuroscience
Nervous System Diseases
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AbstractMicrosatellite expansions are the leading cause of numerous neurodegenerative disorders. Here we demonstrate that GGGGCC and CAG microsatellite repeat RNAs associated with C9orf72 in ALS/FTD and with polyglutamine diseases, respectively, localize to neuritic granules that undergo active transport into distal neuritic segments. In cultured mammalian spinal cord neurons, the presence of neuritic GGGGCC repeat RNA correlates with neuronal branching defects and the repeat RNA localizes to granules that label with FMRP, a transport granule component. Using a Drosophila GGGGCC expansion disease model, we characterize dendritic branching defects that are modulated by FMRP and Orb2. The human orthologues of these modifiers are misregulated in induced pluripotent stem cell-differentiated neurons from GGGGCC expansion carriers. These data suggest that expanded repeat RNAs interact with the mRNA transport and translation machinery, causing transport granule dysfunction. This could be a novel mechanism contributing to the neuronal defects associated with C9orf72 and other microsatellite expansion diseases.
SourceElife. 2015 Dec 9;4. pii: e08881. doi: 10.7554/eLife.08881. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/39847
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© 2015, Schweizer Burguete et al. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Except where otherwise noted, this item's license is described as <p>© 2015, Schweizer Burguete et al. This article is distributed under the terms of the <a href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</a> permitting unrestricted use and redistribution provided that the original author and source are credited.</p>