ArticlePLoS genetics2014
Transcription-associated R-loop formation across the human FMR1 CGG-repeat region.
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 153 papers.
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Who cites it
153 citing papers in PubMed, 235 citations in OpenAlex.
- Deciphering the role of cell-free extrachromosomal circular DNA in human heart failure.Human genomics · 2026Article
- R-loop landscapes in the developing human brain are linked to neural differentiation and cell type-specific transcription.Translational psychiatry · 2026Article
- Mis-spliced FMR1 transcripts in human fragile X syndrome neural progenitors and neurons.Journal of neurodevelopmental disorders · 2026Article
- When R-Loops Go Awry: Genome Instability and Neurological Diseases.The European journal of neuroscience · 2026Review
- Article
- MDS/AML-associated DDX41 helicase facilitates homologous recombination repair by potentially resolving R-loops.Nucleic acids research · 2026Article
- CGG, CAG, and GAA: Genome-wide comparison of the disease linked trinucleotide short tandem repeats.BMC genomics · 2026Article
- 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
- The relevance of RNA-DNA interactions as regulators of physiological functions.Pflugers Archiv : European journal of physiology · 2025Review
- Article
- MSH2 is not required for either maintenance of DNA methylation or repeat contraction at the FMR1 locus in fragile X syndrome or the FXN locus in Friedreich's ataxia.Epigenetics & chromatin · 2025Article
- DNA supercoiling-mediated G4/R-loop formation tunes transcription by controlling the access of RNA polymerase.Nature communications · 2025Article
- Tandem repeat disorders: from diagnosis to emerging therapeutic strategies.Encephalitis (Seoul, Korea) · 2025Article
- Reduced Respiratory Sinus Arrhythmia in Infants with theInternational journal of molecular sciences · 2025Article
- Novel p.Arg534del Mutation and MTHFR C667T Polymorphism in Fragile X Syndrome (FXS) With Autism Spectrum Phenotype: A Case Report.Case reports in genetics · 2025Article
- R-loops as a trigger for intra- and extrachromosomal DNA amplification in cancer.Frontiers in cell and developmental biology · 2025Review
93 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Expansion of a trinucleotide (CGG) repeat element within the 5' untranslated region (5'UTR) of the human FMR1 gene is responsible for a number of heritable disorders operating through distinct pathogenic mechanisms: gene silencing for fragile X syndrome (>200 CGG) and RNA toxic gain-of-function for FXTAS (∼ 55-200 CGG). Existing models have focused almost exclusively on post-transcriptional mechanisms, but co-transcriptional processes could also contribute to the molecular dysfunction of FMR1. We have observed that transcription through the GC-rich FMR1 5'UTR region favors R-loop formation, with the nascent (G-rich) RNA forming a stable RNA:DNA hybrid with the template DNA strand, thereby displacing the non-template DNA strand. Using DNA:RNA (hybrid) immunoprecipitation (DRIP) of genomic DNA from cultured human dermal fibroblasts with both normal (∼ 30 CGG repeats) and premutation (55<CGG<200 repeats) alleles, we provide evidence for FMR1 R-loop formation in human genomic DNA. Using a doxycycline (DOX)-inducible episomal system in which both the CGG-repeat and transcription frequency can be varied, we further show that R-loop formation increases with higher expression levels. Finally, non-denaturing bisulfite mapping of the displaced single-stranded DNA confirmed R-loop formation at the endogenous FMR1 locus and further indicated that R-loops formed over CGG repeats may be prone to structural complexities, including hairpin formation, not commonly associated with other R-loops. These observations introduce a new molecular feature of the FMR1 gene that is directly affected by CGG-repeat expansion and is likely to be involved in the associated cellular dysfunction.
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