ArticleThe Journal of biological chemistry2013
The disease-associated r(GGGGCC)n repeat from the C9orf72 gene forms tract length-dependent uni- and multimolecular RNA G-quadruplex structures.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 209 papers.
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Who cites it
209 citing papers in PubMed, 318 citations in OpenAlex.
- RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- Insights into X-linked Dystonia-Parkinsonism and Spinocerebellar Ataxia type 36 Through the Lens of Amyotrophic Lateral Sclerosis/Frontotemporal Dementia.Molecular neurobiology · 2026Review
- Direct targeting of C9ORF72 repeat RNA with fluorinated antisense oligonucleotides.Nucleic acids research · 2026Article
- Microprotein Regulates G-quadruplex Driven RNA Aggregation.bioRxiv : the preprint server for biology · 2026Article
- Article
- Thermally activated history-dependent homogenization of G-quadruplexes in an ALS/FTD-associated gene.Biophysical journal · 2026Article
- G-Quadruplexes Abet Neuronal Burnout in ALS and FTD.Antioxidants (Basel, Switzerland) · 2025Review
- Investigation of possible G-quadruplex formation by GU- and GA-rich repeats and their role in translation.RNA biology · 2025Article
- The molecular mechanism of uptake and cell-to-cell transmission of arginine-containing dipeptide repeat proteins.bioRxiv : the preprint server for biology · 2025Article
- Thermally activated irreversible homogenization of G-quadruplexes in an ALS/FTD-associated gene.bioRxiv : the preprint server for biology · 2025Article
- Visualization of liquid-liquid phase transitions using a tiny G-quadruplex binding protein.Nature communications · 2025Article
- Visualization of liquid-liquid phase transitions using a tiny G-quadruplex binding protein.bioRxiv : the preprint server for biology · 2025Article
- Crystal structures of distinct parallel and antiparallel DNA G-quadruplexes reveal structural polymorphism in C9orf72 G4C2 repeats.Nucleic acids research · 2025Article
- Homotypic RNA clustering accompanies a liquid-to-solid transition inside the core of multi-component biomolecular condensates.Nature chemistry · 2025Article
- RNA G-quadruplex structure targeting and imaging: recent advances and future directions.RNA (New York, N.Y.) · 2025Review
- Review
- Review
- High-Sensitivity Fluorescence-Based Detection of Reverse Transcriptase Read-Through of GC-Rich Short Tandem Repeat RNA.Analytical chemistry · 2025Article
- G-Quadruplex Structures Formed by Human Telomere andInternational journal of molecular sciences · 2025Review
- Biomolecular Condensates Can Enhance Homotypic RNA Clustering.bioRxiv : the preprint server for biology · 2025Article
149 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Certain DNA and RNA sequences can form G-quadruplexes, which can affect promoter activity, genetic instability, RNA splicing, translation, and neurite mRNA localization. Amyotrophic lateral sclerosis and frontotemporal dementia were recently shown to be caused by expansion of a (GGGGCC)n·(GGCCCC)n repeat in the C9orf72 gene. Mutant r(GGGGCC)n-containing transcripts aggregate in nuclear foci possibly sequestering repeat-binding proteins, suggesting a toxic RNA pathogenesis. We demonstrate that the r(GGGGCC)n RNA but not the C-rich r(GGCCCC)n RNA forms extremely stable uni- and multimolecular parallel G-quadruplex structures (up to 95 °C). Multimolecular G-quadruplex formation is influenced by repeat number and RNA concentration. MBNL1, a splicing factor that is sequestered in myotonic dystrophy patients by binding to expanded r(CUG)n repeat hairpins, does not bind the C9orf72 repeats, but the splicing factor ASF/SF2 can bind the r(GGGGCC)n repeat. Because multimolecular G-quadruplexes are enhanced by repeat length, RNA-RNA interactions facilitated by G-quadruplex formation at expanded repeats might influence transcript aggregation and foci formation in amyotrophic lateral sclerosis-frontotemporal dementia cells. Tract length-dependent G-quadruplex formation by the C9orf72 RNA should be considered when assessing the role of this repeat in C9orf72 gene activity, protein binding, transcript foci formation, and translation of the C9orf72 product, including the noncanonical repeat-associated non-ATG translation (RAN translation) into pathologic dipeptide repeats, as well as any oligonucleotide repeat-based therapy.
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