ArticleAmerican journal of human genetics1998
The GAA triplet-repeat expansion in Friedreich ataxia interferes with transcription and may be associated with an unusual DNA structure.
Article in American journal of human genetics, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers.
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Who cites it
152 citing papers in PubMed, 379 citations in OpenAlex.
- Epigenetic therapy for Friedreich ataxia.Annals of neurology · 2014Trial
- Altered gene expression and DNA damage in peripheral blood cells from Friedreich's ataxia patients: cellular model of pathology.PLoS genetics · 2010Trial
- Therapeutic activity of a hematopoietic stem cell-delivered cell-penetrating frataxin in Friedreich's ataxia models.Cell reports. Medicine · 2026Article
- Transcription and cohesin direct domain boundary spatial positioning and are linked to Friedreich's ataxia.Molecular cell · 2026Article
- Friedreich ataxia transcriptomic dysregulation and identification of cell type-specific biomarkers: A systematic review and meta-analysis.bioRxiv : the preprint server for biology · 2026Article
- Unrecognized high prevalence of expanded composite repeats in Friedreich ataxia.Human molecular genetics · 2026Article
- Human pluripotent stem cell models of Friedreich's ataxia: innovations, considerations, and future perspectives.Stem cell research & therapy · 2026Review
- Recent developments in Friedreich's ataxia: a state-of-the-art review.Brain communications · 2026Review
- How DNA secondary structures drive replication fork instability.DNA repair · 2025Review
- A global perspective on research advances and future challenges in Friedreich ataxia.Nature reviews. Neurology · 2025Review
- TheBrain communications · 2025Article
- Stabilization of expandable DNA repeats by the replication factor Mcm10 promotes cell viability.Nature communications · 2024Article
- Triplex H-DNA structure: the long and winding road from the discovery to its role in human disease.NAR molecular medicine · 2024Article
- Skeletal Muscle Involvement in Friedreich Ataxia.International journal of molecular sciences · 2024Review
- AAGGG repeat expansions triggerScience advances · 2024Article
- Anatomical and functional analysis of the corticospinal tract in an FRDA mouse model.bioRxiv : the preprint server for biology · 2024Article
- The Regulation of the Disease-Causing GeneCells · 2024Review
- Detection of alternative DNA structures and its implications for human disease.Molecular cell · 2023Review
- Patient-derived iPSC models of Friedreich ataxia: a new frontier for understanding disease mechanisms and therapeutic application.Translational neurodegeneration · 2023Review
- Article
92 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Friedreich ataxia (FRDA), an autosomal recessive, neurodegenerative disease is the most common inherited ataxia. The vast majority of patients are homozygous for an abnormal expansion of a polymorphic GAA triplet repeat in the first intron of the X25 gene, which encodes a mitochondrial protein, frataxin. Cellular degeneration in FRDA may be caused by mitochondrial dysfunction, possibly due to abnormal iron accumulation, as observed in yeast cells deficient for a frataxin homologue. Using RNase protection assays, we have shown that patients homozygous for the expansion have a marked deficiency of mature X25 mRNA. The mechanism(s) by which the intronic GAA triplet expansion results in this reduction of X25 mRNA is presently unknown. No evidence was found for abnormal splicing of the expanded intron 1. Using cloned repeat sequences from FRDA patients, we show that the GAA repeat per se interferes with in vitro transcription in a length-dependent manner, with both prokaryotic and eukaryotic enzymes. This interference was most pronounced in the physiological orientation of transcription, when synthesis of the GAA-rich transcript was attempted. These results are consistent with the observed negative correlation between triplet-repeat length and the age at onset of disease. Using in vitro chemical probing strategies, we also show that the GAA triplet repeat adopts an unusual DNA structure, demonstrated by hyperreactivity to osmium tetroxide, hydroxylamine, and diethyl pyrocarbonate. These results raise the possibility that the GAA triplet-repeat expansion may result in an unusual yet stable DNA structure that interferes with transcription, ultimately leading to a cellular deficiency of frataxin.
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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.