ArticleThe EMBO journal2016
Minor intron splicing is regulated by FUS and affected by ALS-associated FUS mutants.
Article in The EMBO journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 118 citations in OpenAlex.
- Dysregulation of mitochondrial bioenergetics, RNA processing, and cellular stress responses in FUS-ALS: a multi-dataset transcriptomic perspective.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Article
- ALS-associated exitron splicing produces UBQLN2 isoforms with distinct properties.bioRxiv : the preprint server for biology · 2026Article
- Gene Targeted Therapies for Neurodegenerative Disorders: Strategies and Implications in ALS and SMA.Genes · 2026Review
- Breaking β-sheets in FUS prion-like domain preserves phase separation and function but prevents aggregation and toxicity.bioRxiv : the preprint server for biology · 2026Article
- Compartment-specific transcriptome of motor neurons reveals impaired extracellular matrix signaling and activated cell cycle kinases in FUS-ALS.Neurobiology of disease · 2026Article
- Massively parallel assay of human splice variants reveals cis-regulatory drivers of disease-associated and cell type-specific splicing regulation.bioRxiv : the preprint server for biology · 2025Article
- Neuromuscular dysfunction in patient-derived FUSNAR molecular medicine · 2025Article
- Allele-Selective Thiomorpholino Antisense Oligonucleotides as a Therapeutic Approach for Fused-in-Sarcoma Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2024Article
- Expression of Truncated Products at the 5'-Terminal Region of RIPK2 and Evolutive Aspects that Support Their Biological Importance.Genome biology and evolution · 2024Article
- Liquid-liquid phase separation in diseases.MedComm · 2024Review
- G-quadruplexes control hepatitis B virus replication by promoting cccDNA transcription and phase separation in hepatocytes.Nucleic acids research · 2024Article
- Regulation of neuronal circHomer1 biogenesis by PKA/CREB/ERK-mediated pathways and effects of glutamate and dopamine receptor blockade.Research square · 2024Article
- RIP-PEN-seq identifies a class of kink-turn RNAs as splicing regulators.Nature biotechnology · 2024Article
- hnRNPs: roles in neurodevelopment and implication for brain disorders.Frontiers in molecular neuroscience · 2024Review
- Drosha-dependent microRNAs modulate FUS-mediated neurodegeneration in vivo.Nucleic acids research · 2023Article
- Molecular basis of RNA-binding and autoregulation by the cancer-associated splicing factor RBM39.Nature communications · 2023Article
- Minor intron splicing is critical for survival of lethal prostate cancer.Molecular cell · 2023Article
- FUS regulates a subset of snoRNA expression and modulates the level of rRNA modifications.Scientific reports · 2023Article
- FUS Alters circRNA Metabolism in Human Motor Neurons Carrying the ALS-Linked P525L Mutation.International journal of molecular sciences · 2023Article
- Emerging roles of spliceosome in cancer and immunity.Protein & cell · 2022Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fused in sarcoma (FUS) is a ubiquitously expressed RNA-binding protein proposed to function in various RNA metabolic pathways, including transcription regulation, pre-mRNA splicing, RNA transport and microRNA processing. Mutations in the FUS gene were identified in patients with amyotrophic lateral sclerosis (ALS), but the pathomechanisms by which these mutations cause ALS are not known. Here, we show that FUS interacts with the minor spliceosome constituent U11 snRNP, binds preferentially to minor introns and directly regulates their removal. Furthermore, a FUS knockout in neuroblastoma cells strongly disturbs the splicing of minor intron-containing mRNAs, among them mRNAs required for action potential transmission and for functional spinal motor units. Moreover, an ALS-associated FUS mutant that forms cytoplasmic aggregates inhibits splicing of minor introns by trapping U11 and U12 snRNAs in these aggregates. Collectively, our findings suggest a possible pathomechanism for ALS in which mutated FUS inhibits correct splicing of minor introns in mRNAs encoding proteins required for motor neuron survival.
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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.