ArticlePLoS genetics2021
DEAD-box RNA helicase Dbp4/DDX10 is an enhancer of α-synuclein toxicity and oligomerization.
Article in PLoS genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Guanosine 10 methylation by TRMT11-TRMT112 optimizes human mitochondrial tRNAs for efficient translation.Nucleic acids research · 2026Article
- Blm10/PA200-Activated 20S Proteasomes Promote α-Synuclein Degradation and Bypass Proteasome Inhibition in Parkinson's Disease Models.Aging cell · 2026Article
- From Yeast to Therapeutics: Modeling Neurodegenerative Diseases in Saccharomyces cerevisiae.Yeast (Chichester, England) · 2025Review
- Alpha-synuclein regulates nucleolar DNA double-strand break repair in melanoma.Science advances · 2025Article
- Inhibition of 26S proteasome activity by α-synuclein is mediated by the proteasomal chaperone Rpn14/PAAF1.Aging cell · 2024Article
- Article
- Alpha-synuclein regulates nucleolar DNA double-strand break repair in melanoma.bioRxiv : the preprint server for biology · 2024Article
- Saccharomyces cerevisiae as a research tool for RNA-mediated human disease.Wiley interdisciplinary reviews. RNA · 2023Review
- Inter- and intra-chromosomal modulators of the APOE ɛ2 and ɛ4 effects on the Alzheimer's disease risk.GeroScience · 2023Article
- Nuclear α-Synuclein-Derived Cytotoxic Effect via Altered Ribosomal RNA Processing in Primary Mouse Embryonic Fibroblasts.International journal of molecular sciences · 2023Article
- α-Synuclein and Mechanisms of Epigenetic Regulation.Brain sciences · 2023Review
- Role and therapeutic potential of DEAD-box RNA helicase family in colorectal cancer.Frontiers in oncology · 2023Review
- Genetic modifiers of synucleinopathies-lessons from experimental models.Oxford open neuroscience · 2023Review
- RNA Helicases in Microsatellite Repeat Expansion Disorders and Neurodegeneration.Frontiers in genetics · 2022Review
- Synthetic lethal interactions of DEAD/H-box helicases as targets for cancer therapy.Frontiers in oncology · 2022Review
- α-Synuclein Decreases the Abundance of Proteasome Subunits and Alters Ubiquitin Conjugates in Yeast.Cells · 2021Article
- Identification of Two Novel Peptides That Inhibit α-Synuclein Toxicity and Aggregation.Frontiers in molecular neuroscience · 2021Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease is a neurodegenerative disorder associated with misfolding and aggregation of α-synuclein as a hallmark protein. Two yeast strain collections comprising conditional alleles of essential genes were screened for the ability of each allele to reduce or improve yeast growth upon α-synuclein expression. The resulting 98 novel modulators of α-synuclein toxicity clustered in several major categories including transcription, rRNA processing and ribosome biogenesis, RNA metabolism and protein degradation. Furthermore, expression of α-synuclein caused alterations in pre-rRNA transcript levels in yeast and in human cells. We identified the nucleolar DEAD-box helicase Dbp4 as a prominent modulator of α-synuclein toxicity. Downregulation of DBP4 rescued cells from α-synuclein toxicity, whereas overexpression led to a synthetic lethal phenotype. We discovered that α-synuclein interacts with Dbp4 or its human ortholog DDX10, sequesters the protein outside the nucleolus in yeast and in human cells, and stabilizes a fraction of α-synuclein oligomeric species. These findings provide a novel link between nucleolar processes and α-synuclein mediated toxicity with DDX10 emerging as a promising drug target.
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