ArticleNucleic acids research2015
U1 snRNP is mislocalized in ALS patient fibroblasts bearing NLS mutations in FUS and is required for motor neuron outgrowth in zebrafish.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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51 citing papers in PubMed, 80 citations in OpenAlex.
- Excess Met1-linked ubiquitination leads to solid aggregate formation.The EMBO journal · 2026Article
- U1 snRNA interactions with deep intronic sequences regulate splicing of multiple exons of spinal muscular atrophy genes.Frontiers in neuroscience · 2024Article
- Amyotrophic Lateral Sclerosis, FUS and Protein Synthesis Defects.Stem cell reviews and reports · 2023Review
- The identification of high-performing antibodies for RNA-binding protein FUS for use in Western Blot, immunoprecipitation, and immunofluorescence.F1000Research · 2023Article
- Alzheimer's disease-associated U1 snRNP splicing dysfunction causes neuronal hyperexcitability and cognitive impairment.Nature aging · 2022Article
- Conformational change of RNA-helicase DHX30 by ALS/FTD-linked FUS induces mitochondrial dysfunction and cytosolic aggregates.Scientific reports · 2022Article
- Protein network analysis to prioritize key genes in amyotrophic lateral sclerosis.IBRO neuroscience reports · 2022Article
- Zebrafish as a model organism for neurodegenerative disease.Frontiers in molecular neuroscience · 2022Review
- Alternative Splicing in Human Biology and Disease.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Axonal regeneration and sprouting as a potential therapeutic target for nervous system disorders.Neural regeneration research · 2021Review
- The phase separation-dependent FUS interactome reveals nuclear and cytoplasmic function of liquid-liquid phase separation.Nucleic acids research · 2021Article
- ALS-linked FUS mutants affect the localization of U7 snRNP and replication-dependent histone gene expression in human cells.Scientific reports · 2021Article
- Defining the Caprin-1 Interactome in Unstressed and Stressed Conditions.Journal of proteome research · 2021Article
- Trends in Understanding the Pathological Roles of TDP-43 and FUS Proteins.Advances in experimental medicine and biology · 2021Article
- Phylogenetic Comparison and Splicing Analysis of the U1 snRNP-specific Protein U1C in Eukaryotes.Frontiers in molecular biosciences · 2021Article
- Intronic Determinants Coordinate Charme lncRNA Nuclear Activity through the Interaction with MATR3 and PTBP1.Cell reports · 2020Article
- Aberrant interaction of FUS with the U1 snRNA provides a molecular mechanism of FUS induced amyotrophic lateral sclerosis.Nature communications · 2020Article
- Molecular and Cellular Mechanisms Affected in ALS.Journal of personalized medicine · 2020Review
- Article
- FUS ALS-causative mutations impair FUS autoregulation and splicing factor networks through intron retention.Nucleic acids research · 2020Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Mutations in FUS cause amyotrophic lateral sclerosis (ALS), but the molecular pathways leading to neurodegeneration remain obscure. We previously found that U1 snRNP is the most abundant FUS interactor. Here, we report that components of the U1 snRNP core particle (Sm proteins and U1 snRNA), but not the mature U1 snRNP-specific proteins (U1-70K, U1A and U1C), co-mislocalize with FUS to the cytoplasm in ALS patient fibroblasts harboring mutations in the FUS nuclear localization signal (NLS). Similar results were obtained in HeLa cells expressing the ALS-causing FUS R495X NLS mutation, and mislocalization of Sm proteins is RRM-dependent. Moreover, as observed with FUS, knockdown of any of the U1 snRNP-specific proteins results in a dramatic loss of SMN-containing Gems. Significantly, knockdown of U1 snRNP in zebrafish results in motor axon truncations, a phenotype also observed with FUS, SMN and TDP-43 knockdowns. Our observations linking U1 snRNP to ALS patient cells with FUS mutations, SMN-containing Gems, and motor neurons indicate that U1 snRNP is a component of a molecular pathway associated with motor neuron disease. Linking an essential canonical splicing factor (U1 snRNP) to this pathway provides strong new evidence that splicing defects may be involved in pathogenesis and that this pathway is a potential therapeutic target.
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