ArticleNature communications2017
SRSF1-dependent nuclear export inhibition of C9ORF72 repeat transcripts prevents neurodegeneration and associated motor deficits.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 147 citations in OpenAlex.
- ALS-associated exitron splicing produces UBQLN2 isoforms with distinct properties.bioRxiv : the preprint server for biology · 2026Article
- The contribution of short tandem repeats to splicing variation in the human cortex.bioRxiv : the preprint server for biology · 2026Article
- Microprotein Regulates G-quadruplex Driven RNA Aggregation.bioRxiv : the preprint server for biology · 2026Article
- Genetic epidemiology of C9orf72 repeat expansion associated amyotrophic lateral sclerosis in Hungary.Molecular medicine (Cambridge, Mass.) · 2026Article
- Antisense Dipeptide Repeat Proteins Drive Widescale Purine Metabolism Aberration inInternational journal of molecular sciences · 2026Article
- C9orf72-ALS mutation drives basal mitophagy impairments in iNeurons.Frontiers in cellular neuroscience · 2026Article
- Aberrant splicing exonizes C9orf72 repeat expansion in ALS/FTD.Nature neuroscience · 2025Article
- Targeting GeneInternational journal of molecular sciences · 2025Review
- High-throughput screen of 100 000 small molecules in C9ORF72 ALS neurons identifies spliceosome modulators that mobilize G4C2 repeat RNA into nuclear export and repeat associated non-canonical translation.Nucleic acids research · 2025Article
- Akkermansia mono-colonization modulates microglia and astrocytes in a strain specific manner.Journal of neuroinflammation · 2025Article
- C9ORF72 poly-PR disrupts expression of ALS/FTD-implicated STMN2 through SRSF7.Acta neuropathologica communications · 2025Article
- Controlled by disorder: Phosphorylation modulates SRSF1 domain availability for spliceosome assembly.Protein science : a publication of the Protein Society · 2025Article
- Amyotrophic lateral sclerosis caused by hexanucleotide repeat expansions in C9orf72: from genetics to therapeutics.The Lancet. Neurology · 2025Review
- The promise of gene therapy in common types of dementia.BioImpacts : BI · 2025Review
- Article
- SRSF1 Is Required for Mitochondrial Homeostasis and Thermogenic Function in Brown Adipocytes Through its Control of Ndufs3 Splicing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Artificial microRNA suppresses C9ORF72 variants and decreases toxic dipeptide repeat proteins in vivo.Gene therapy · 2024Article
- Phenylalanine-tRNA aminoacylation is compromised by ALS/FTD-associated C9orf72 C4G2 repeat RNA.Nature communications · 2023Article
- The master energy homeostasis regulator PGC-1α exhibits an mRNA nuclear export function.Nature communications · 2023Article
- TDP-43 pathology in Drosophila induces glial-cell type specific toxicity that can be ameliorated by knock-down of SF2/SRSF1.PLoS genetics · 2023Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
26 authors at 4 institutions in 2 countries.
Funding
Abstract
Hexanucleotide repeat expansions in the C9ORF72 gene are the commonest known genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Expression of repeat transcripts and dipeptide repeat proteins trigger multiple mechanisms of neurotoxicity. How repeat transcripts get exported from the nucleus is unknown. Here, we show that depletion of the nuclear export adaptor SRSF1 prevents neurodegeneration and locomotor deficits in a Drosophila model of C9ORF72-related disease. This intervention suppresses cell death of patient-derived motor neuron and astrocytic-mediated neurotoxicity in co-culture assays. We further demonstrate that either depleting SRSF1 or preventing its interaction with NXF1 specifically inhibits the nuclear export of pathological C9ORF72 transcripts, the production of dipeptide-repeat proteins and alleviates neurotoxicity in Drosophila, patient-derived neurons and neuronal cell models. Taken together, we show that repeat RNA-sequestration of SRSF1 triggers the NXF1-dependent nuclear export of C9ORF72 transcripts retaining expanded hexanucleotide repeats and reveal a novel promising therapeutic target for neuroprotection.
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