ArticleHuman molecular genetics2011
Genes and pathways affected by CAG-repeat RNA-based toxicity in Drosophila.
Article in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
- Insights into dentatorubral-pallidoluysian atrophy from a new Drosophila model of disease.Neurobiology of disease · 2025Article
- A phenotypically robust model of spinal and bulbar muscular atrophy in Drosophila.Journal of neuroscience research · 2024Article
- Gelation of cytoplasmic expanded CAG RNA repeats suppresses global protein synthesis.Nature chemical biology · 2023Article
- DnaJC7 in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2022Review
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- The Molecular Basis of Spinocerebellar Ataxia Type 7.Frontiers in neuroscience · 2022Review
- Hsc70-4 aggravates PolyQ-mediated neurodegeneration by modulating NF-κB mediated immune response inFrontiers in molecular neuroscience · 2022Article
- Insect Behavioral Change and the Potential Contributions of Neuroinflammation-A Call for Future Research.Genes · 2021Review
- Article
- Differential toxicity of ataxin-3 isoforms in Drosophila models of Spinocerebellar Ataxia Type 3.Neurobiology of disease · 2019Article
- Altered Levels and Isoforms of Tau and Nuclear Membrane Invaginations in Huntington's Disease.Frontiers in cellular neuroscience · 2019Review
- Review
- Spinocerebellar ataxias: prospects and challenges for therapy development.Nature reviews. Neurology · 2018Review
- Inhibition of NF-κB in astrocytes is sufficient to delay neurodegeneration induced by proteotoxicity in neurons.Journal of neuroinflammation · 2018Article
- Impaired Wnt signaling in dopamine containing neurons is associated with pathogenesis in a rotenone triggered Drosophila Parkinson's disease model.Scientific reports · 2018Article
- Protein sequestration as a normal function of long noncoding RNAs and a pathogenic mechanism of RNAs containing nucleotide repeat expansions.Human genetics · 2017Review
- RNA toxicity and foci formation in microsatellite expansion diseases.Current opinion in genetics & development · 2017Review
- Review
- Article
- The first crystal structures of RNA-PNA duplexes and a PNA-PNA duplex containing mismatches--toward anti-sense therapy against TREDs.Nucleic acids research · 2016Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Spinocerebellar ataxia type 3 is one of the polyglutamine (polyQ) diseases, which are caused by a CAG-repeat expansion within the coding region of the associated genes. The CAG repeat specifies glutamine, and the expanded polyQ domain mutation confers dominant toxicity on the protein. Traditionally, studies have focused on protein toxicity in polyQ disease mechanisms. Recent findings, however, demonstrate that the CAG-repeat RNA, which encodes the toxic polyQ protein, also contributes to the disease in Drosophila. To provide insights into the nature of the RNA toxicity, we extracted brain-enriched RNA from flies expressing a toxic CAG-repeat mRNA (CAG100) and a non-toxic interrupted CAA/G mRNA repeat (CAA/G105) for microarray analysis. This approach identified 160 genes that are differentially expressed specifically in CAG100 flies. Functional annotation clustering analysis revealed several broad ontologies enriched in the CAG100 gene list, including iron ion binding and nucleotide binding. Intriguingly, transcripts for the Hsp70 genes, a powerful suppressor of polyQ and other human neurodegenerative diseases, were also upregulated. We therefore tested and showed that upregulation of heat shock protein 70 mitigates CAG-repeat RNA toxicity. We then assessed whether other modifiers of the pathogenic, expanded Ataxin-3 polyQ protein could also modify the CAG-repeat RNA toxicity. This approach identified the co-chaperone Tpr2, the transcriptional regulator Dpld, and the RNA-binding protein Orb2 as modifiers of both polyQ protein toxicity and CAG-repeat RNA-based toxicity. These findings suggest an overlap in the mechanisms of RNA and protein-based toxicity, providing insights into the pathogenicity of the RNA in polyQ disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.