Retrotransposon activation contributes to fragile X premutation rCGG-mediated neurodegeneration
Open accessAbstract
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder associated with fragile X premutation carriers. Previous studies have shown that fragile X rCGG repeats are sufficient to cause neurodegeneration and that the rCGG-repeat-binding proteins Pur α and heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 could modulate rCGG-mediated neuronal toxicity. Mobile genetic elements or their remnants populate the genomes, and the activities of these elements are tightly controlled for the fitness of host genomes in different organisms. Here we provide both biochemical and genetic evidence to show that the activation of a specific retrotransposon, gypsy, can modulate rCGG-mediated neurodegeneration in an FXTAS Drosophila model. We find that one of the rCGG-repeat-binding proteins, hnRNP A2/B1, is involved in this process via interaction with heterochromatin protein 1. Knockdown of gypsy RNA by RNAi could suppress the neuronal toxicity caused by rCGG repeats. These data together point to a surprisingly active role for retrotransposition in neurodegeneration.
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L1 activity has been implicated in a variety of age-related disorders, including cancer and neurodegeneration.
“L1 activity has been implicated in a variety of age-related disorders12, including cancer7,13 and neurodegeneration14,15.”
From SIRT6 represses LINE1 retrotransposons by ribosylating KAP1 but this repression fails with stress and age (2014) · cites this paper as [15]
The Discussion reports that retrotransposon activation contributes to neurodegeneration in a fragile X fly model, supporting the neurodegeneration portion at the level of retrotransposons generally. It identifies gypsy, not L1, as the retrotransposon whose reduction suppresses neuronal toxicity; its discussion of cancer likewise does not implicate L1 specifically. The paper therefore does not support the broader claim about L1 activity across age-related disorders. (LLM, conf=0.87)
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Cites
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- Authors
- Tan, H., Qurashi, A., Poidevin, M., Nelson, D. L., Li, H., & Jin, P.
- Affiliations
- Emory University (US)
- Baylor College of Medicine (US)
- Huazhong University of Science and Technology (CN)
- Corresponding author
- Li, H.
- Jin, P.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-09-22
- Volume
- 21
- Issue
- 1
- Pages
- 57-65
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- PMC
- PMC3235010
- OpenAlex
- W2099637873
- Cited by
- 78
- References
- 2
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 8 · 2020: 11 · 2019: 11 · 2018: 7 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 4 · 2013: 3 · 2012: 5
- FWCI
- 2.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Molecular Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Ataxia Foundation
- China Scholarship Council
- National Institute of Mental Health (R01MH076090)
- National Institute of Neurological Disorders and Stroke (R01NS051630, R21NS067461)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- fragile X premutation, fragile X-associated tremor/ataxia syndrome, retrotransposon activation, gypsy retrotransposon, neurodegeneration, HNRNPA2B1, Purα, HP1, Drosophila model, mobile genetic elements, RNA interference
- MeSH terms
- Animals, Disease Models, Animal, Drosophila, Eye, Female, Humans, Male, Neurons, Retroelements, Neurodegenerative Diseases, Trinucleotide Repeat Expansion, Drosophila Proteins, Heterogeneous-Nuclear Ribonucleoprotein Group A-B
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