ArticleBrain : a journal of neurology2019
Widespread FUS mislocalization is a molecular hallmark of amyotrophic lateral sclerosis.
Article in Brain : a journal of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
92 citing papers in PubMed, 190 citations in OpenAlex.
- RNA-Binding Motif Protein 3 as a Therapeutic and Prognostic Target for Drug Discovery.Current issues in molecular biology · 2026Review
- Intron retention in health and amyotrophic lateral sclerosis.Brain : a journal of neurology · 2026Review
- ThebioRxiv : the preprint server for biology · 2026Article
- Competition between protein-RNA clustering and phase separation drives re-entrant phase behavior of hnRNPA1.Nature communications · 2026Article
- γ-Radiation induces region-specific subcellular alterations of amyotrophic lateral sclerosis and frontotemporal dementia markers in swine brain.Scientific reports · 2026Article
- Hypoxic stress is an early pathogenic event in human VCP-mutant ALS astrocytes.Stem cell reports · 2026Article
- From development to disease: the neuronal role of hnRNPs through the lens ofFrontiers in cell and developmental biology · 2026Review
- Decoding the interactions and functions of non-coding RNA with artificial intelligence.Nature reviews. Molecular cell biology · 2025Review
- 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
- ALS-associated RNA-binding proteins promote UNC13A transcription through REST downregulation.The EMBO journal · 2025Article
- An alternative cytoplasmic SFPQ isoform with reduced phase separation potential is up-regulated in ALS.Science advances · 2025Article
- Comprehensive protein datasets and benchmarking for liquid-liquid phase separation studies.Genome biology · 2025Article
- FUS Mislocalization Rewires a Cortical Gene Network to Drive Cognitive and Behavioral Impairment in ALS.medRxiv : the preprint server for health sciences · 2025Article
- Review
- Unraveling Molecular Targets for Neurodegenerative Diseases ThroughInternational journal of molecular sciences · 2025Review
- Advancements in genetic research and RNA therapy strategies for amyotrophic lateral sclerosis (ALS): current progress and future prospects.Journal of neurology · 2025Review
- Paraspeckle Component 1: a multifunctional RNA binding protein.American journal of cancer research · 2025Review
- Article
- Nuclear pore dysfunction and disease: a complex opportunity.Nucleus (Austin, Tex.) · 2024Review
- Aberrant protein aggregation in amyotrophic lateral sclerosis.Journal of neurology · 2024Review
32 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Mutations causing amyotrophic lateral sclerosis (ALS) clearly implicate ubiquitously expressed and predominantly nuclear RNA binding proteins, which form pathological cytoplasmic inclusions in this context. However, the possibility that wild-type RNA binding proteins mislocalize without necessarily becoming constituents of cytoplasmic inclusions themselves remains relatively unexplored. We hypothesized that nuclear-to-cytoplasmic mislocalization of the RNA binding protein fused in sarcoma (FUS), in an unaggregated state, may occur more widely in ALS than previously recognized. To address this hypothesis, we analysed motor neurons from a human ALS induced-pluripotent stem cell model caused by the VCP mutation. Additionally, we examined mouse transgenic models and post-mortem tissue from human sporadic ALS cases. We report nuclear-to-cytoplasmic mislocalization of FUS in both VCP-mutation related ALS and, crucially, in sporadic ALS spinal cord tissue from multiple cases. Furthermore, we provide evidence that FUS protein binds to an aberrantly retained intron within the SFPQ transcript, which is exported from the nucleus into the cytoplasm. Collectively, these data support a model for ALS pathogenesis whereby aberrant intron retention in SFPQ transcripts contributes to FUS mislocalization through their direct interaction and nuclear export. In summary, we report widespread mislocalization of the FUS protein in ALS and propose a putative underlying mechanism for this process.
Indexed as
Identifiers
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.