ArticleNature communications2015
ALS-causative mutations in FUS/TLS confer gain and loss of function by altered association with SMN and U1-snRNP.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers, 1 of them a synthesis that pooled it.
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
147 citing papers in PubMed, 1 synthesis or guideline pooled it, 236 citations in OpenAlex.
- Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.Neuroscience · 2019Pooled it
- CHCHD2 and CHCHD10 promoted autophagic clearance of protein aggregates via GABARAPs.Autophagy · 2026Article
- Hierarchical Nuclear Architecture in Pre-mRNA Splicing: From IDRs to Speckles and Meshworks.International journal of molecular sciences · 2026Review
- A single-cell, long-read, isoform-resolved case-control study of FTD reveals cell-type-specific and broad splicing dysregulation in human brain.Cell reports · 2025Article
- ALS-associated RNA-binding proteins promote UNC13A transcription through REST downregulation.The EMBO journal · 2025Article
- Amyotrophic Lateral Sclerosis: Focus on Cytoplasmic Trafficking and Proteostasis.Molecular neurobiology · 2025Review
- RNA dysregulation in neurodegenerative diseases.The EMBO journal · 2025Review
- Intermolecular energy migration via homoFRET captures the modulation in the material property of phase-separated biomolecular condensates.Nature communications · 2024Article
- Article
- Poly-GR repeats associated with ALS/FTD geneScience signaling · 2024Article
- AAV-NRIP gene therapy ameliorates motor neuron degeneration and muscle atrophy in ALS model mice.Skeletal muscle · 2024Article
- FUS reads histone H3K36me3 to regulate alternative polyadenylation.Nucleic acids research · 2024Article
- The roles of FUS-RNA binding domain and low complexity domain in RNA-dependent phase separation.Structure (London, England : 1993) · 2024Article
- hnRNPs: roles in neurodevelopment and implication for brain disorders.Frontiers in molecular neuroscience · 2024Review
- Mimicking hypomethylation of FUS requires liquid-liquid phase separation to induce synaptic dysfunctions.Acta neuropathologica communications · 2023Article
- FUS-dependent microRNA deregulations identify TRIB2 as a druggable target for ALS motor neurons.iScience · 2023Article
- Analysis of asymptomatic Drosophila models for ALS and SMA reveals convergent impact on functional protein complexes linked to neuro-muscular degeneration.BMC genomics · 2023Article
- Regulation of Biomolecular Condensates by Poly(ADP-ribose).Chemical reviews · 2023Review
- Cytoplasmic aggregation of mutant FUS causes multistep RNA splicing perturbations in the course of motor neuron pathology.Nucleic acids research · 2023Article
- Bi-allelic SNAPC4 variants dysregulate global alternative splicing and lead to neuroregression and progressive spastic paraparesis.American journal of human genetics · 2023Article
87 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
16 authors at 4 institutions in 1 country.
Funding
Abstract
The RNA-binding protein FUS/TLS, mutation in which is causative of the fatal motor neuron disease amyotrophic lateral sclerosis (ALS), is demonstrated to directly bind to the U1-snRNP and SMN complexes. ALS-causative mutations in FUS/TLS are shown to abnormally enhance their interaction with SMN and dysregulate its function, including loss of Gems and altered levels of small nuclear RNAs. The same mutants are found to have reduced association with U1-snRNP. Correspondingly, global RNA analysis reveals a mutant-dependent loss of splicing activity, with ALS-linked mutants failing to reverse changes caused by loss of wild-type FUS/TLS. Furthermore, a common FUS/TLS mutant-associated RNA splicing signature is identified in ALS patient fibroblasts. Taken together, these studies establish potentially converging disease mechanisms in ALS and spinal muscular atrophy, with ALS-causative mutants acquiring properties representing both gain (dysregulation of SMN) and loss (reduced RNA processing mediated by U1-snRNP) of function.
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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.