ArticleActa neuropathologica2019
C9orf72 arginine-rich dipeptide proteins interact with ribosomal proteins in vivo to induce a toxic translational arrest that is rescued by eIF1A.
Article in Acta neuropathologica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 123 citations in OpenAlex.
- Karyoptosis mediates cell death and neurodegeneration upon proteotoxic stress.Nature communications · 2026Article
- The intrinsic disorder challenge for AlphaFold: A case study of G3BP1 and pathogenic peptide.iScience · 2026Article
- At the core of the interaction: Probing charged side chains in flexible protein regions with simultaneous nuclear magnetic resonance experiments.Protein science : a publication of the Protein Society · 2026Article
- Article
- Dysregulated neuronal mRNA transport and translation in FTD/ALS.NPJ dementia · 2026Review
- The telomeric valine-arginine dipeptide repeat protein changes state to diffuse staining in mitosis and represses in vitro translation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Aberrant splicing exonizes C9orf72 repeat expansion in ALS/FTD.Nature neuroscience · 2025Article
- Translational regulation in stress biology.Nature cell biology · 2025Review
- Canonical translation factors eIF1A and eIF5B modulate the initiation step of repeat-associated non-AUG translation.Nucleic acids research · 2025Article
- Loss of Pol III repressor Maf1 in neurons promotes longevity by preventing the age-related decline in 5S rRNA and translation.PLoS biology · 2025Article
- Targeting GeneInternational journal of molecular sciences · 2025Review
- RNA dysregulation in neurodegenerative diseases.The EMBO journal · 2025Review
- A high-fidelity CRISPR-Cas13 system improves abnormalities associated with C9ORF72-linked ALS/FTD.Nature communications · 2025Article
- C9orf72-linked arginine-rich dipeptide repeats aggravate pathological phase separation of G3BP1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Poly-GP accumulation due to C9orf72 loss of function induces motor neuron apoptosis through autophagy and mitophagy defects.Autophagy · 2024Article
- Understanding Amyotrophic Lateral Sclerosis: Pathophysiology, Diagnosis, and Therapeutic Advances.International journal of molecular sciences · 2024Review
- Poly-GR repeats associated with ALS/FTD geneScience signaling · 2024Article
- The nuclear import receptor Kapβ2 modifies neurotoxicity mediated by poly(GR) in C9orf72-linked ALS/FTD.Communications biology · 2024Article
- Cell-Penetrating and Enzyme-Responsive Peptides for Targeted Cancer Therapy: Role of Arginine Residue Length on Cell Penetration and In Vivo Systemic Toxicity.ACS applied materials & interfaces · 2024Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 7 institutions in 5 countries.
Funding
Abstract
A GGGGCC hexanucleotide repeat expansion within the C9orf72 gene is the most common genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia. Sense and antisense repeat-containing transcripts undergo repeat-associated non-AUG-initiated translation to produce five dipeptide proteins (DPRs). The polyGR and polyPR DPRs are extremely toxic when expressed in Drosophila neurons. To determine the mechanism that mediates this toxicity, we purified DPRs from the Drosophila brain and used mass spectrometry to identify the in vivo neuronal DPR interactome. PolyGR and polyPR interact with ribosomal proteins, and inhibit translation in both human iPSC-derived motor neurons, and adult Drosophila neurons. We next performed a screen of 81 translation-associated proteins in GGGGCC repeat-expressing Drosophila to determine whether this translational repression can be overcome and if this impacts neurodegeneration. Expression of the translation initiation factor eIF1A uniquely rescued DPR-induced toxicity in vivo, indicating that restoring translation is a potential therapeutic strategy. These data directly implicate translational repression in C9orf72 repeat-induced neurodegeneration and identify eIF1A as a novel modifier of C9orf72 repeat toxicity.
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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.