ArticleMolecular cell2016
CGG Repeat-Associated Non-AUG Translation Utilizes a Cap-Dependent Scanning Mechanism of Initiation to Produce Toxic Proteins.
Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
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Who cites it
120 citing papers in PubMed, 185 citations in OpenAlex.
- Two dipeptide repeat proteins are produced from mammalian telomeric RNA previously thought to be a long non-coding RNA.RNA biology · 2026Review
- Article
- Altered neuronal start codon stringency favors cap-independent repeat-associated non-AUG translation.Nucleic acids research · 2026Article
- Altered neuronal start codon stringency favors cap-independent repeat-associated non-AUG translation.bioRxiv : the preprint server for biology · 2026Article
- Upstream non-AUG initiation and ribosomal -1 frameshifting in ATXN8OS CTA/CTG repeat-associated translation.Nucleic acids research · 2026Article
- The role of FMR1 mRNA structure on the efficiency of non-canonical translation of toxic polyglycine protein.Nucleic acids research · 2026Article
- Translation of expanded CGG repeats in LRP12 associated oculopharyngodistal myopathy.Acta neuropathologica communications · 2026Article
- Article
- Blocking RAN translation without altering repeat RNAs rescuesScience (New York, N.Y.) · 2026Article
- Integrative transcriptome-wide association analyses reveal PRKCG-linked GABAergic dysfunction in Fragile X-associated tremor/ataxia syndrome.Nature communications · 2026Article
- IGF2BPs directly regulate the noncanonical translation of toxic proteins from mutant FMR1 mRNA containing expanded CGG repeats.Nature communications · 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
- Canonical translation factors eIF1A and eIF5B modulate the initiation step of repeat-associated non-AUG translation.Nucleic acids research · 2025Article
- Cryptic intronic transcriptional initiation generates efficient endogenous mRNA templates for C9orf72-associated RAN translation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Endogenous retrovirus-like proteins recruit UBQLN2 to stress granules and shape their functional biology.Science advances · 2025Article
- Article
- Advances on the Mechanisms and Therapeutic Strategies in Non-coding CGG Repeat Expansion Diseases.Molecular neurobiology · 2024Review
- Translation of HIV-1 unspliced RNA is regulated by 5' untranslated region structure.Journal of virology · 2024Article
- Single-molecule tracking reveals dynamic regulation of ribosomal scanning.Science advances · 2024Article
- Sequence composition changes in short tandem repeats: heterogeneity, detection, mechanisms and clinical implications.Nature reviews. Genetics · 2024Review
60 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Repeat-associated non-AUG (RAN) translation produces toxic polypeptides from nucleotide repeat expansions in the absence of an AUG start codon and contributes to neurodegenerative disorders such as ALS and fragile X-associated tremor/ataxia syndrome. How RAN translation occurs is unknown. Here we define the critical sequence and initiation factors that mediate CGG repeat RAN translation in the 5' leader of fragile X mRNA, FMR1. Our results reveal that CGG RAN translation is 30%-40% as efficient as AUG-initiated translation, is m(7)G cap and eIF4E dependent, requires the eIF4A helicase, and is strongly influenced by repeat length. However, it displays a dichotomous requirement for initiation site selection between reading frames, with initiation in the +1 frame, but not the +2 frame, occurring at near-cognate start codons upstream of the repeat. These data support a model in which RAN translation at CGG repeats uses cap-dependent ribosomal scanning, yet bypasses normal requirements for start codon selection.
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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.