ArticleNature neuroscience2020
A native function for RAN translation and CGG repeats in regulating fragile X protein synthesis.
Article in Nature neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 76 citations in OpenAlex.
- The role of FMR1 mRNA structure on the efficiency of non-canonical translation of toxic polyglycine protein.Nucleic acids research · 2026Article
- Mis-spliced FMR1 transcripts in human fragile X syndrome neural progenitors and neurons.Journal of neurodevelopmental disorders · 2026Article
- Translation of expanded CGG repeats in LRP12 associated oculopharyngodistal myopathy.Acta neuropathologica communications · 2026Article
- Autophagy controls the hippocampal postsynaptic organization and affects cognition in a mouse model of Fragile X syndrome.Molecular psychiatry · 2026Article
- IGF2BPs directly regulate the noncanonical translation of toxic proteins from mutant FMR1 mRNA containing expanded CGG repeats.Nature communications · 2025Article
- Longitudinal Analysis of Neuroradiological Biomarkers for Fragile X-Associated Tremor/Ataxia Syndrome and Implications for Clinical Trials.Annals of neurology · 2025Article
- Autophagy controls the hippocampal postsynaptic organization and affects cognition in a mouse model of Fragile X syndrome.Research square · 2025Article
- Machine learning-based proteomics profiling of ALS identifies downregulation of RPS29 that maintains protein homeostasis and STMN2 level.Communications biology · 2025Article
- Tandem repeat disorders: from diagnosis to emerging therapeutic strategies.Encephalitis (Seoul, Korea) · 2025Article
- Beyond Repetition: The Role of Gray Zone Alleles in the Upregulation ofInternational journal of molecular sciences · 2025Article
- High-Sensitivity Fluorescence-Based Detection of Reverse Transcriptase Read-Through of GC-Rich Short Tandem Repeat RNA.Analytical chemistry · 2025Article
- Trinucleotide repeat expansion and RNA dysregulation in fragile X syndrome: emerging therapeutic approaches.RNA (New York, N.Y.) · 2025Review
- Genetic diagnosis of three intellectually disabled individuals in a pedigree and insights into fragile X syndrome diagnosis.Frontiers in neuroscience · 2025Article
- Review
- Advances on the Mechanisms and Therapeutic Strategies in Non-coding CGG Repeat Expansion Diseases.Molecular neurobiology · 2024Review
- A phenome-wide association study of methylated GC-rich repeats identifies a GCC repeat expansion in AFF3 associated with intellectual disability.Nature genetics · 2024Article
- AAGGG repeat expansions triggerScience advances · 2024Article
- CGG repeats in the human FMR1 gene regulate mRNA localization and cellular stress in developing neurons.Cell reports · 2024Article
- Epigenetic insights into Fragile X Syndrome.Frontiers in cell and developmental biology · 2024Review
- Review
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Repeat-associated non-AUG-initiated translation of expanded CGG repeats (CGG RAN) from the FMR1 5'-leader produces toxic proteins that contribute to neurodegeneration in fragile X-associated tremor/ataxia syndrome. Here we describe how unexpanded CGG repeats and their translation play conserved roles in regulating fragile X protein (FMRP) synthesis. In neurons, CGG RAN acts as an inhibitory upstream open reading frame to suppress basal FMRP production. Activation of mGluR5 receptors enhances FMRP synthesis. This enhancement requires both the CGG repeat and CGG RAN initiation sites. Using non-cleaving antisense oligonucleotides (ASOs), we selectively blocked CGG RAN. This ASO blockade enhanced endogenous FMRP expression in human neurons. In human and rodent neurons, CGG RAN-blocking ASOs suppressed repeat toxicity and prolonged survival. These findings delineate a native function for CGG repeats and RAN translation in regulating basal and activity-dependent FMRP synthesis, and they demonstrate the therapeutic potential of modulating CGG RAN translation in fragile X-associated 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.