ArticleNucleic acids research2024
Ribosomal quality control factors inhibit repeat-associated non-AUG translation from GC-rich repeats.
Article in Nucleic acids research, 2024. 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, 18 citations in OpenAlex.
- RAN Translation-Coupled Decay of theInternational journal of molecular sciences · 2026Article
- Upstream non-AUG initiation and ribosomal -1 frameshifting in ATXN8OS CTA/CTG repeat-associated translation.Nucleic acids research · 2026Article
- Microglial Dysfunction Induced by C9ORF72 Dipeptide Repeat Proteins: Biomarker and Therapeutic Perspectives.International journal of molecular sciences · 2026Review
- Blocking RAN translation without altering repeat RNAs rescuesScience (New York, N.Y.) · 2026Article
- Quality control and signaling pathways at stalled ribosomes.Experimental & molecular medicine · 2026Review
- IGF2BPs directly regulate the noncanonical translation of toxic proteins from mutant FMR1 mRNA containing expanded CGG repeats.Nature communications · 2025Article
- CRISPR activation of the ribosome-associated quality control factor ASCC3 ameliorates fragile X syndrome phenotypes in mice.Science translational medicine · 2025Article
- Defective Ribosome Recycling: A Bridge Between Translation Fidelity, Organelle Dysfunction, and Diseases: Exploring How Flawed Ribosome Recycling Factors Impact Ribosome Metabolism and Organelle Homeostasis, Leading to Human Diseases.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Article
- Structural Features of 5' Untranslated Region in Translational Control of Eukaryotes.International journal of molecular sciences · 2025Review
- 5'-UTR G-Quadruplex-Mediated Translation Regulation in Eukaryotes: Current Understanding and Methodological Challenges.International journal of molecular sciences · 2025Review
- TGF-β2 Induces Ribosome Activity, Alters Ribosome Composition and Inhibits IRES-Mediated Translation in Chondrocytes.International journal of molecular sciences · 2024Article
- Reconstitution of C9orf72 GGGGCC repeat-associated non-AUG translation with purified human translation factors.Scientific reports · 2023Article
- Lost in Translation: When the Rules Do Not Apply.Wiley interdisciplinary reviews. RNAReview
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
A GGGGCC (G4C2) hexanucleotide repeat expansion in C9ORF72 causes amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD), while a CGG trinucleotide repeat expansion in FMR1 leads to the neurodegenerative disorder Fragile X-associated tremor/ataxia syndrome (FXTAS). These GC-rich repeats form RNA secondary structures that support repeat-associated non-AUG (RAN) translation of toxic proteins that contribute to disease pathogenesis. Here we assessed whether these same repeats might trigger stalling and interfere with translational elongation. We find that depletion of ribosome-associated quality control (RQC) factors NEMF, LTN1 and ANKZF1 markedly boost RAN translation product accumulation from both G4C2 and CGG repeats while overexpression of these factors reduces RAN production in both reporter assays and C9ALS/FTD patient iPSC-derived neurons. We also detected partially made products from both G4C2 and CGG repeats whose abundance increased with RQC factor depletion. Repeat RNA sequence, rather than amino acid content, is central to the impact of RQC factor depletion on RAN translation-suggesting a role for RNA secondary structure in these processes. Together, these findings suggest that ribosomal stalling and RQC pathway activation during RAN translation inhibits the generation of toxic RAN products. We propose augmenting RQC activity as a therapeutic strategy in GC-rich repeat expansion disorders.
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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.