ArticlePLoS genetics2014
R-loops associated with triplet repeat expansions promote gene silencing in Friedreich ataxia and fragile X syndrome.
Article in PLoS genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 231 papers, 1 of them a synthesis that pooled it.
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Who cites it
231 citing papers in PubMed, 1 synthesis or guideline pooled it, 351 citations in OpenAlex.
- The role of R-loops-mediated epigenetic regulation in genome stability maintenance and disease pathogenesis: a systematic review.Epigenetics · 2026Pooled it
- Focal ischemia induces genome-wide accumulation of R-loops in the brain.Molecular therapy. Nucleic acids · 2026Article
- R-PLA enables enhanced detection of R-loops in mammalian cells using proximity ligation.Cell reports methods · 2026Article
- RNA-binding proteins TDP-43 and FUS promote R-loop resolution and regulate transcription termination.The Journal of biological chemistry · 2026Article
- R-loop landscapes in the developing human brain are linked to neural differentiation and cell type-specific transcription.Translational psychiatry · 2026Article
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- Article
- The PARP1-EXD2 axis orchestrates R-loop resolution to safeguard genome stability.Nature chemical biology · 2026Article
- Recent developments in Friedreich's ataxia: a state-of-the-art review.Brain communications · 2026Review
- Article
- IGF2BPs directly regulate the noncanonical translation of toxic proteins from mutant FMR1 mRNA containing expanded CGG repeats.Nature communications · 2025Article
- Long-read sequencing reveals extensivebioRxiv : the preprint server for biology · 2025Article
- Heterochromatin-based silencing of a foreign tandem repeat inbioRxiv : the preprint server for biology · 2025Article
- The CGG triplet repeat binding protein 1 counteracts R-loop induced transcription-replication stress.EMBO reports · 2025Article
- Participants in Transcription-Replication Conflict and Their Role in Formation and Resolution of R-Loops.International journal of molecular sciences · 2025Review
- Update on R-loops in genomic integrity: Formation, functions, and implications for human diseases.Genes & diseases · 2025Review
- Core biological principles and tools stemming from basic Arabidopsis research.The Plant cell · 2025Review
- Complex determinants of R-loop formation at transposable elements and major DNA satellites.Genetics · 2025Article
- Somatic instability of the FGF14-SCA27B GAA•TTC repeat reveals a marked expansion bias in the cerebellum.Brain : a journal of neurology · 2025Article
- Tandem repeat disorders: from diagnosis to emerging therapeutic strategies.Encephalitis (Seoul, Korea) · 2025Article
171 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Friedreich ataxia (FRDA) and Fragile X syndrome (FXS) are among 40 diseases associated with expansion of repeated sequences (TREDs). Although their molecular pathology is not well understood, formation of repressive chromatin and unusual DNA structures over repeat regions were proposed to play a role. Our study now shows that RNA/DNA hybrids (R-loops) form in patient cells on expanded repeats of endogenous FXN and FMR1 genes, associated with FRDA and FXS. These transcription-dependent R-loops are stable, co-localise with repressive H3K9me2 chromatin mark and impede RNA Polymerase II transcription in patient cells. We investigated the interplay between repressive chromatin marks and R-loops on the FXN gene. We show that decrease in repressive H3K9me2 chromatin mark has no effect on R-loop levels. Importantly, increasing R-loop levels by treatment with DNA topoisomerase inhibitor camptothecin leads to up-regulation of repressive chromatin marks, resulting in FXN transcriptional silencing. This provides a direct molecular link between R-loops and the pathology of TREDs, suggesting that R-loops act as an initial trigger to promote FXN and FMR1 silencing. Thus R-loops represent a common feature of nucleotide expansion disorders and provide a new target for therapeutic interventions.
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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.