ArticleProceedings of the National Academy of Sciences of the United States of America2023
Repeat-associated non-AUG translation induces cytoplasmic aggregation of CAG repeat-containing RNAs.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Phototriggered Morphological and Compositional Change of UGGAA Repeat RNA Foci by Photoswitchable RNA-Binding Ligand.Angewandte Chemie (International ed. in English) · 2026Article
- Microprotein Regulates G-quadruplex Driven RNA Aggregation.bioRxiv : the preprint server for biology · 2026Article
- Condensate protein aggregation in ALS/FTD is regulated by GGGGCC-repeat RNA scaffolds.Nature structural & molecular biology · 2026Article
- Blocking RAN translation without altering repeat RNAs rescuesScience (New York, N.Y.) · 2026Article
- Molecular drivers of RNA phase separation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Water-detected NMR allows dynamic observations of repeat-expansion RNA condensates.Nature chemistry · 2025Article
- A distal promoter and aberrant splicing enable canonical translation of out-of-frame proteins in Huntington's disease.bioRxiv : the preprint server for biology · 2025Article
- RNA-driven phase transitions in biomolecular condensates.Molecular cell · 2024Review
- NMR structures and magnetic force spectroscopy studies of small molecules binding to models of an RNA CAG repeat expansion.bioRxiv : the preprint server for biology · 2024Article
- Review
- Article
- Structural polymorphism of the nucleic acids in pentanucleotide repeats associated with the neurological disorder CANVAS.The Journal of biological chemistry · 2024Article
- CAG repeat expansions create splicing acceptor sites and produce aberrant repeat-containing RNAs.Molecular cell · 2024Article
- RNA repeats stall translation.Nature chemical biology · 2023Article
- CAG repeat expansions create splicing acceptor sites and produce aberrant repeat-containing RNAs.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
CAG trinucleotide repeat expansions cause several neurodegenerative diseases, including Huntington's disease and spinocerebellar ataxia. RNAs with expanded CAG repeats contribute to disease in two unusual ways. First, these repeat-containing RNAs may agglomerate in the nucleus as foci that sequester several RNA-binding proteins. Second, these RNAs may undergo aberrant repeat-associated non-AUG (RAN) translation in multiple frames and produce aggregation-prone proteins. The relationship between RAN translation and RNA foci, and their relative contributions to cellular dysfunction, are unclear. Here, we show that CAG repeat-containing RNAs that undergo RAN translation first accumulate at nuclear foci and, over time, are exported to the cytoplasm. In the cytoplasm, these RNAs are initially dispersed but, upon RAN translation, aggregate with the RAN translation products. These RNA-RAN protein agglomerates sequester various RNA-binding proteins and are associated with the disruption of nucleocytoplasmic transport and cell death. In contrast, RNA accumulation at nuclear foci alone does not produce discernable defects in nucleocytoplasmic transport or cell viability. Inhibition of RAN translation prevents cytoplasmic RNA aggregation and alleviates cell toxicity. Our findings demonstrate that RAN translation-induced RNA-protein aggregation correlates with the key pathological hallmarks observed in disease and suggest that cytoplasmic RNA aggregation may be an underappreciated phenomenon in CAG trinucleotide repeat expansion disorders.
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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.