ArticleNeuron2020
Nucleocytoplasmic Proteomic Analysis Uncovers eRF1 and Nonsense-Mediated Decay as Modifiers of ALS/FTD C9orf72 Toxicity.
Article in Neuron, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00821132 (Identification of Genes Causing Familial ALS or Increasing Risk for Sporadic ALS and ALS With Frontotemporal Dementia and Understanding Disease Mechanism.), which is not on this map. Cited by 54 papers.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Identification of Genes Causing Familial ALS or Increasing Risk for Sporadic ALS and ALS With Frontotemporal Dementia and Understanding Disease Mechanism.
Who cites it
54 citing papers in PubMed, 87 citations in OpenAlex.
- RAN Translation-Coupled Decay of theInternational journal of molecular sciences · 2026Article
- Short RNA chaperones promote aggregation-resistant TDP-43 conformers to mitigate neurodegeneration.Science (New York, N.Y.) · 2026Article
- The function of mRNA quality control in aging and age-related diseases.The Journal of biological chemistry · 2026Review
- Article
- Supercharging-enhanced nDIA-MS enables global profiling of drug-induced proteome solubility shifts.Nature communications · 2026Article
- Defining RNA oligonucleotides that reverse deleterious phase transitions of RNA-binding proteins with prion-like domains.Molecular cell · 2026Article
- TDP-43-dependent mis-splicing of KCNQ2 triggers intrinsic neuronal hyperexcitability in ALS/FTD.Nature neuroscience · 2025Article
- Review
- Gene therapy breakthroughs in ALS: a beacon of hope for 20% of ALS patients.Translational neurodegeneration · 2025Review
- Context-dependent Interactors Regulate TDP-43 Dysfunction in ALS/FTLD.bioRxiv : the preprint server for biology · 2025Article
- Longitudinal multi-omics in alpha-synuclein Drosophila model discriminates disease- from age-associated pathologies in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- RuvBL1/2 reduce toxic dipeptide repeat protein burden in multiple models of C9orf72-ALS/FTD.Life science alliance · 2025Article
- RNA dysregulation in neurodegenerative diseases.The EMBO journal · 2025Review
- Opposing roles of p38α-mediated phosphorylation and PRMT1-mediated arginine methylation in driving TDP-43 proteinopathy.Cell reports · 2025Article
- Reduced UPF1 levels in senescence impair nonsense-mediated mRNA decay.Communications biology · 2025Article
- The ALS-associated co-chaperone DNAJC7 mediates neuroprotection against proteotoxic stress by modulating HSF1 activity.bioRxiv : the preprint server for biology · 2024Article
- Pathogenic tau induces an adaptive elevation in mRNA translation rate at early stages of disease.Aging cell · 2024Article
- Traumatic injury causes selective degeneration and TDP-43 mislocalization in human iPSC-derivedbioRxiv : the preprint server for biology · 2024Article
- Invertebrate genetic models of amyotrophic lateral sclerosis.Frontiers in molecular neuroscience · 2024Review
- Histone post-translational modification and heterochromatin alterations in neurodegeneration: revealing novel disease pathways and potential therapeutics.Frontiers in molecular neuroscience · 2024Review
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
The most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is a hexanucleotide repeat expansion in C9orf72 (C9-HRE). While RNA and dipeptide repeats produced by C9-HRE disrupt nucleocytoplasmic transport, the proteins that become redistributed remain unknown. Here, we utilized subcellular fractionation coupled with tandem mass spectrometry and identified 126 proteins, enriched for protein translation and RNA metabolism pathways, which collectively drive a shift toward a more cytosolic proteome in C9-HRE cells. Among these was eRF1, which regulates translation termination and nonsense-mediated decay (NMD). eRF1 accumulates within elaborate nuclear envelope invaginations in patient induced pluripotent stem cell (iPSC) neurons and postmortem tissue and mediates a protective shift from protein translation to NMD-dependent mRNA degradation. Overexpression of eRF1 and the NMD driver UPF1 ameliorate C9-HRE toxicity in vivo. Our findings provide a resource for proteome-wide nucleocytoplasmic alterations across neurodegeneration-associated repeat expansion mutations and highlight eRF1 and NMD as therapeutic targets in C9orf72-associated ALS and/or FTD.
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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.