ArticleHuman molecular genetics2013
ALS mutant FUS disrupts nuclear localization and sequesters wild-type FUS within cytoplasmic stress granules.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 160 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
160 citing papers in PubMed, 270 citations in OpenAlex.
- Pharmacogenetic interactions in amyotrophic lateral sclerosis: a step closer to a cure?The pharmacogenomics journal · 2020Trial
- Stress granules at the crossroads of the proteostasis network.RNA biology · 2026Review
- From optical control to translational readiness: an evidence-tiered framework for optogenetics in neuromuscular and neurological disorders.Materials today. Bio · 2026Review
- Synaptic Proteostasis in Health and Disease.Journal of neurochemistry · 2026Review
- Shuttle and stabilize: H1.2-FUS complex in amyotrophic lateral sclerosis pathogenesis.Neural regeneration research · 2026Article
- LINE-1 Retrotransposons and Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2026Review
- Review
- Proteasomal-dependent CHK1 degradation leads to DNA damage accumulation in ALS cellular model systems.Cell death & disease · 2026Article
- RNArchitects: how hnRNPs shape neuronal landscapes.Brain : a journal of neurology · 2026Review
- RNA-binding proteins TDP-43 and FUS promote R-loop resolution and regulate transcription termination.The Journal of biological chemistry · 2026Article
- Splicing the narrative: alternative TARDBP splicing and its relation to neurodegeneration in ALS and FTD.The Journal of clinical investigation · 2026Review
- Human FUS is toxic via association with RNA polymerase II in Drosophila.Cell death & disease · 2026Article
- Target-stabilized base editors enable robust high-fidelity RNA editing.Nature communications · 2026Article
- FUS is an N1- and N6-methyladenosine-binding protein.Nucleic acids research · 2026Article
- Review
- Prematurely Aged Human Microglia Exhibit Impaired Stress Response and Defective Nucleocytoplasmic Shuttling of ALS Associated FUS.Aging cell · 2025Article
- Unveiling the Spatiotemporal dynamics of stress granule phase transition: A key mechanism governing neuronal fate in acute ischemic stroke.Molecular biology reports · 2025Review
- RNA Binding Mechanism of the FUS Zinc Finger in Concert with Its Flanking Intrinsically Disordered Region.Journal of chemical information and modeling · 2025Article
- Antisense oligonucleotide jacifusen for FUS-ALS: an investigator-initiated, multicentre, open-label case series.Lancet (London, England) · 2025Article
- Single-cell RNA-sequencing reveals early mitochondrial dysfunction unique to motor neurons shared across FUS- and TARDBP-ALS.Nature communications · 2025Article
100 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
Mutations in the gene encoding Fused in Sarcoma (FUS) cause amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. FUS is a predominantly nuclear DNA- and RNA-binding protein that is involved in RNA processing. Large FUS-immunoreactive inclusions fill the perikaryon of surviving motor neurons of ALS patients carrying mutations at post-mortem. This sequestration of FUS is predicted to disrupt RNA processing and initiate neurodegeneration. Here, we demonstrate that C-terminal ALS mutations disrupt the nuclear localizing signal (NLS) of FUS resulting in cytoplasmic accumulation in transfected cells and patient fibroblasts. FUS mislocalization is rescued by the addition of the wild-type FUS NLS to mutant proteins. We also show that oxidative stress recruits mutant FUS to cytoplasmic stress granules where it is able to bind and sequester wild-type FUS. While FUS interacts with itself directly by protein-protein interaction, the recruitment of FUS to stress granules and interaction with PABP are RNA dependent. These findings support a two-hit hypothesis, whereby cytoplasmic mislocalization of FUS protein, followed by cellular stress, contributes to the formation of cytoplasmic aggregates that may sequester FUS, disrupt RNA processing and initiate motor neuron degeneration.
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What OpenQuestion holds
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.