ArticleScientific reports2020
Proteomics analysis of FUS mutant human motoneurons reveals altered regulation of cytoskeleton and other ALS-linked proteins via 3'UTR binding.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
- Proteomic profile of Laser-dissected Motoneurons, Ependymal Cell Layer and Dorsal Root Ganglia after Spinal Cord Injury in the Rat.Scientific data · 2026Article
- Exploring the bidirectional causal relationship between Autism Spectrum Disorder and Schizophrenia using Mendelian randomization.Medicine · 2025Article
- Review
- HuD impairs neuromuscular junctions and induces apoptosis in human iPSC and Drosophila ALS models.Nature communications · 2024Article
- Mutation of the ALS-/FTD-Associated RNA-Binding Protein FUS Affects Axonal Development.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Integrative proteomics highlight presynaptic alterations and c-Jun misactivation as convergent pathomechanisms in ALS.Acta neuropathologica · 2023Article
- Blood RNA transcripts reveal similar and differential alterations in fundamental cellular processes in Alzheimer's disease and other neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- FUS Alters circRNA Metabolism in Human Motor Neurons Carrying the ALS-Linked P525L Mutation.International journal of molecular sciences · 2023Article
- Digital color-coded molecular barcoding reveals dysregulation of common FUS and FMRP targets in soma and neurites of ALS mutant motoneurons.Cell death discovery · 2023Article
- Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases.International journal of molecular sciences · 2022Review
- TheThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Synaptic dysfunction in ALS and FTD: anatomical and molecular changes provide insights into mechanisms of disease.Frontiers in molecular neuroscience · 2022Review
- ALS-related FUS mutations alter axon growth in motoneurons and affect HuD/ELAVL4 and FMRP activity.Communications biology · 2021Article
- FUS-ALS mutants alter FMRP phase separation equilibrium and impair protein translation.Science advances · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Increasing evidence suggests that in Amyotrophic Lateral Sclerosis (ALS) mutated RNA binding proteins acquire aberrant functions, leading to altered RNA metabolism with significant impact on encoded protein levels. Here, by taking advantage of a human induced pluripotent stem cell-based model, we aimed to gain insights on the impact of ALS mutant FUS on the motoneuron proteome. Label-free proteomics analysis by mass-spectrometry revealed upregulation of proteins involved in catabolic processes and oxidation-reduction, and downregulation of cytoskeletal proteins and factors directing neuron projection. Mechanistically, proteome alteration does not correlate with transcriptome changes. Rather, we observed a strong correlation with selective binding of mutant FUS to target mRNAs in their 3'UTR. Novel validated targets, selectively bound by mutant FUS, include genes previously involved in familial or sporadic ALS, such as VCP, and regulators of membrane trafficking and cytoskeleton remodeling, such as ASAP1. These findings unveil a novel mechanism by which mutant FUS might intersect other pathogenic pathways in ALS patients' motoneurons.
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