ArticlePLoS biology2011
A yeast model of FUS/TLS-dependent cytotoxicity.
Article in PLoS biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers, 1 of them a synthesis that pooled it.
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Who cites it
142 citing papers in PubMed, 1 synthesis or guideline pooled it, 1 citations in OpenAlex.
- Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.Neuroscience · 2019Pooled it
- High-throughput screening approach identifies substrate-selective Hsp104 variants that counter amyloid seeding with diminished off-target effects.Molecular cell · 2026Article
- RNA-Binding Protein TAF15 Suppresses Toxicity in a Yeast Model of FUS Proteinopathy.Journal of fungi (Basel, Switzerland) · 2026Article
- The function of mRNA quality control in aging and age-related diseases.The Journal of biological chemistry · 2026Review
- Article
- Multiplex neurodegeneration proteotoxicity platform reveals DNAJB6 promotes non-toxic FUS condensate gelation and inhibits neurotoxicity.Nature communications · 2025Article
- Yeast Prions: Discovery, Nature, Cellular Manipulation and Implication.Journal of microbiology and biotechnology · 2025Review
- RNA dysregulation in neurodegenerative diseases.The EMBO journal · 2025Review
- TDP43 autoregulation gives rise to dominant negative isoforms that are tightly controlled by transcriptional and post-translational mechanisms.Cell reports · 2025Article
- Direct and Indirect Protein Interactions Link FUS Aggregation to Histone Post-Translational Modification Dysregulation and Growth Suppression in an ALS/FTD Yeast Model.Journal of fungi (Basel, Switzerland) · 2025Article
- An adenine model of inborn metabolism errors alters TDP-43 aggregation and reduces its toxicity in yeast revealing insights into protein misfolding diseases.Microbial cell (Graz, Austria) · 2025Article
- TDP43 autoregulation gives rise to shortened isoforms that are tightly controlled by both transcriptional and post-translational mechanisms.bioRxiv : the preprint server for biology · 2024Article
- Expression of Wild-Type and Mutant Human TDP-43 in Yeast Inhibits TOROID (TORC1 Organized in Inhibited Domain) Formation and Autophagy Proportionally to the Levels of TDP-43 Toxicity.International journal of molecular sciences · 2024Article
- The Role of mRNA Quality Control in the Aging ofMolecules and cells · 2023Review
- Amyloidogenic propensity of self-assembling peptides and their adjuvant potential for use as DNA vaccines.Acta biomaterialia · 2023Article
- Prions in Microbes: The Least in the Most.Journal of microbiology (Seoul, Korea) · 2023Review
- Tuning Hsp104 specificity to selectively detoxify α-synuclein.Molecular cell · 2023Article
- Saccharomyces cerevisiae as a research tool for RNA-mediated human disease.Wiley interdisciplinary reviews. RNA · 2023Review
- Probing the drivers ofmBio · 2023Article
- Genipin prevents alpha-synuclein aggregation and toxicity by affecting endocytosis, metabolism and lipid storage.Nature communications · 2023Article
82 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
FUS/TLS is a nucleic acid binding protein that, when mutated, can cause a subset of familial amyotrophic lateral sclerosis (fALS). Although FUS/TLS is normally located predominantly in the nucleus, the pathogenic mutant forms of FUS/TLS traffic to, and form inclusions in, the cytoplasm of affected spinal motor neurons or glia. Here we report a yeast model of human FUS/TLS expression that recapitulates multiple salient features of the pathology of the disease-causing mutant proteins, including nuclear to cytoplasmic translocation, inclusion formation, and cytotoxicity. Protein domain analysis indicates that the carboxyl-terminus of FUS/TLS, where most of the ALS-associated mutations are clustered, is required but not sufficient for the toxicity of the protein. A genome-wide genetic screen using a yeast over-expression library identified five yeast DNA/RNA binding proteins, encoded by the yeast genes ECM32, NAM8, SBP1, SKO1, and VHR1, that rescue the toxicity of human FUS/TLS without changing its expression level, cytoplasmic translocation, or inclusion formation. Furthermore, hUPF1, a human homologue of ECM32, also rescues the toxicity of FUS/TLS in this model, validating the yeast model and implicating a possible insufficiency in RNA processing or the RNA quality control machinery in the mechanism of FUS/TLS mediated toxicity. Examination of the effect of FUS/TLS expression on the decay of selected mRNAs in yeast indicates that the nonsense-mediated decay pathway is probably not the major determinant of either toxicity or suppression.
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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.