Files and links (1)
Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
GGGGCC microsatellite RNA is neuritically localized, induces branching defects, and perturbs transport granule function
eLife, v 4
09 Dec 2015
PMID: 26650351
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Microsatellite expansions are the leading cause of numerous neurodegenerative disorders. Here we demonstrate that GGGGCC and CAG microsatellite repeat RNAs associated with C9orf72 in amyotrophic lateral sclerosis/frontotemporal dementia 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 fragile X mental retardation protein (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 orthologs of these modifiers are misregulated in induced pluripotent stem cell-differentiated neurons (iPSNs) from GGGGCC expansion carriers. These data suggest that expanded repeat RNAs interact with the messenger RNA 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.
Metrics
Details
- Title
- GGGGCC microsatellite RNA is neuritically localized, induces branching defects, and perturbs transport granule function
- Creators
- Alondra Schweizer Burguete - Univ Penn, Dept Biol, Philadelphia, PA 19104 USASandra Almeida - Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USAFen-Biao Gao - Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USARobert Kalb - Univ Penn, Childrens Hosp Philadelphia, Sch Med, Div Neurol,Dept Pediat, Philadelphia, PA 19104 USAMichael R. Akins - Drexel UniversityNancy M. Bonini - Univ Penn, Dept Biol, Philadelphia, PA 19104 USA
- Publication Details
- eLife, v 4
- Publisher
- Elife Sciences Publications Ltd
- Number of pages
- 23
- Grant note
- T32AG000255; R21AG042179 / National Institute on Aging; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) F32NS067902; R01NS079725; R21NS077909; R01NS052325; R01NS073660 / National Institute of Neurological Disorders and Stroke; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) R00MH090237 / National Institute of Mental Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) T32AG000255 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) R01NS052325 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology
- Web of Science ID
- WOS:000373809200001
- Scopus ID
- 2-s2.0-84956943850
- Other Identifier
- 991019168879604721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biology