ArticleScientific reports2015
Anti-sense DNA d(GGCCCC)n expansions in C9ORF72 form i-motifs and protonated hairpins.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 85 citations in OpenAlex.
- The Prospective Regulatory Functions of lncRNAs and Their ceRNA Networks in the Development of Motor Neurons and Associated Diseases.Biomolecules · 2026Review
- Indirect identification of genomic G-quadruplexes via a small protein probe that specifically recognizes C-rich single-stranded DNA.Nucleic acids research · 2026Article
- The evolutionary entanglement of flipons with zinc fingers and retroelements has engendered a large family of Z-DNA and G-quadruplex binding proteins.Open biology · 2025Article
- Zfp106 binds to G-quadruplex RNAs and inhibits RAN translation and formation of RNA foci caused by G4C2 repeats.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Antisense RNA C9orf72 hexanucleotide repeat associated with amyotrophic lateral sclerosis and frontotemporal dementia forms a triplex-like structure and binds small synthetic ligand.Nucleic acids research · 2024Article
- Dimeric structures of DNA ATTTC repeats promoted by divalent cations.Nucleic acids research · 2024Article
- Insight into Tetramolecular DNA G-Quadruplexes Associated with ALS and FTLD: Cation Interactions and Formation of Higher-Ordered Structure.International journal of molecular sciences · 2023Article
- Article
- Red light-emitting short Mango-based system enables tracking a mycobacterial small noncoding RNA in infected macrophages.Nucleic acids research · 2023Article
- G-Quadruplexes in Repeat Expansion Disorders.International journal of molecular sciences · 2023Review
- Review
- Novel eGZ-motif formed by regularly extruded guanine bases in a left-handed Z-DNA helix as a major motif behind CGG trinucleotide repeats.Nucleic acids research · 2022Article
- Interactome screening of C9orf72 dipeptide repeats reveals VCP sequestration and functional impairment by polyGA.Brain : a journal of neurology · 2022Article
- RNA Deregulation in Amyotrophic Lateral Sclerosis: The Noncoding Perspective.International journal of molecular sciences · 2021Review
- Therapeutic Potential of Polyphenols in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia.Antioxidants (Basel, Switzerland) · 2021Review
- The Simple Biology of Flipons and Condensates Enhances the Evolution of Complexity.Molecules (Basel, Switzerland) · 2021Review
- Supramolecular Polymorphism of (GInternational journal of molecular sciences · 2021Article
- Secondary structural choice of DNA and RNA associated with CGG/CCG trinucleotide repeat expansion rationalizes the RNA misprocessing in FXTAS.Scientific reports · 2021Article
- Long non-coding RNAs in motor neuron development and disease.Journal of neurochemistry · 2021Review
- SFPQ regulates the accumulation of RNA foci and dipeptide repeat proteins from the expanded repeat mutation inJournal of cell science · 2021Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The G4C2 hexanucleotide repeat expansion mutation (HREM) in C9ORF72, represents the most common mutation associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Three main disease mechanisms have been proposed to date: C9ORF72 haploinsufficiency, RNA toxicity, and accumulation of dipeptide repeat proteins. Pure GC content of the HREM potentially enables the formation of various non-B DNA structures such as G-quadruplexes and i-motifs. These structures are proposed to act as promoters and regulatory elements affecting replication, transcription and translation of the surrounding region. G-quadruplexes have already been shown on the G-rich sense DNA and RNA strands (G4C2)n, the structure of the anti-sense (G2C4)n strand remains unresolved. Similar C-rich sequences may, under acidic conditions, form i-motifs consisting of two parallel duplexes in a head to tail orientation held together by hemi-protonated C(+)-C pairs. We show that d(G2C4)n repeats do form i-motif and protonated hairpins even under near-physiological conditions. Rather than forming a DNA duplex, i-motifs persist even in the presence of the sense strand. This preferential formation of G-quadruplex and i-motif/hairpin structures over duplex DNA, may explain HREM replicational and transcriptional instability. Furthermore, i-motifs/hairpins can represent a novel pharmacological target for C9ORF72 associated ALS and FTLD.
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