ArticlePLoS biology2011
Molecular determinants and genetic modifiers of aggregation and toxicity for the ALS disease protein FUS/TLS.
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 302 papers, 1 of them a synthesis that pooled it.
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Who cites it
302 citing papers in PubMed, 1 synthesis or guideline pooled it, 466 citations in OpenAlex.
- Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.Neuroscience · 2019Pooled it
- Phase separation in neurodegenerative disorders: a metabolic perspective on protein aggregation and therapeutic targeting.Translational neurodegeneration · 2026Review
- RNA G-quadruplexes function as a tunable switch of FUS phase separation.Nucleic acids research · 2026Article
- 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
- Article
- Defining RNA oligonucleotides that reverse deleterious phase transitions of RNA-binding proteins with prion-like domains.Molecular cell · 2026Article
- Heterogeneous Folding Intermediates Govern the Conformational Pathway of the RNA Recognition Motif Domain of the Ewing Sarcoma Protein.Biomolecules · 2025Article
- From Yeast to Therapeutics: Modeling Neurodegenerative Diseases in Saccharomyces cerevisiae.Yeast (Chichester, England) · 2025Review
- Multiplex neurodegeneration proteotoxicity platform reveals DNAJB6 promotes non-toxic FUS condensate gelation and inhibits neurotoxicity.Nature communications · 2025Article
- Nuclear-import receptors remodel the dilute phase to suppress phase transitions of RNA-binding proteins with prion-like domains.bioRxiv : the preprint server for biology · 2025Article
- Review
- RNA G-Quadruplexes Function as a Tunable Switch of FUS Phase Separation.bioRxiv : the preprint server for biology · 2025Article
- Computational investigation of the sequence context of arginine/glycine-rich motifs in the human proteome.BMC genomics · 2025Article
- Matrin-3 forms spherical and wormlike assemblies that are modulated by RNA binding and ALS/FTD-associated mutations.Molecular cell · 2025Article
- Elucidation of the Molecular Interaction Network Underlying Full-Length FUS Conformational Transitions and Its Phase Separation Using Atomistic Simulations.The journal of physical chemistry. B · 2025Article
- RNA-binding proteins in ALS and FTD: from pathogenic mechanisms to therapeutic insights.Molecular neurodegeneration · 2025Review
- Engineered Biomolecular Condensates Limit Tobacco Mosaic Virus Accumulation and Symptom Development.Molecular plant pathology · 2025Article
- RNA binding proteins (RBPs) on genetic stability and diseases.Global medical genetics · 2025Review
- The role of nucleation in sickle cell pathophysiology: opportunities for innovative treatments.Annals of medicine and surgery (2012) · 2025Review
242 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
TDP-43 and FUS are RNA-binding proteins that form cytoplasmic inclusions in some forms of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Moreover, mutations in TDP-43 and FUS are linked to ALS and FTLD. However, it is unknown whether TDP-43 and FUS aggregate and cause toxicity by similar mechanisms. Here, we exploit a yeast model and purified FUS to elucidate mechanisms of FUS aggregation and toxicity. Like TDP-43, FUS must aggregate in the cytoplasm and bind RNA to confer toxicity in yeast. These cytoplasmic FUS aggregates partition to stress granule compartments just as they do in ALS patients. Importantly, in isolation, FUS spontaneously forms pore-like oligomers and filamentous structures reminiscent of FUS inclusions in ALS patients. FUS aggregation and toxicity requires a prion-like domain, but unlike TDP-43, additional determinants within a RGG domain are critical for FUS aggregation and toxicity. In further distinction to TDP-43, ALS-linked FUS mutations do not promote aggregation. Finally, genome-wide screens uncovered stress granule assembly and RNA metabolism genes that modify FUS toxicity but not TDP-43 toxicity. Our findings suggest that TDP-43 and FUS, though similar RNA-binding proteins, aggregate and confer disease phenotypes via distinct mechanisms. These differences will likely have important therapeutic implications.
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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.