ArticleThe Journal of biological chemistry2014
TMPyP4 porphyrin distorts RNA G-quadruplex structures of the disease-associated r(GGGGCC)n repeat of the C9orf72 gene and blocks interaction of RNA-binding proteins.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 219 citations in OpenAlex.
- Exclusion of RNA-binding domains from G-quadruplex condensates by G-quadruplex ligands.RSC chemical biology · 2026Article
- Metal-triggered topology switching in bipyridine-modified DNA G-quadruplexes.Nucleic acids research · 2026Article
- RNA-Focused DNA-Encoded Library Construction, Screening, and Integration of Docking Identify Bioactive Ligands of Pathogenic r(GbioRxiv : the preprint server for biology · 2025Article
- L-RNA Aptamer-Based Tools for G-Quadruplex Structure: Identification, Characterization, and Application.Accounts of chemical research · 2025Article
- Epstein-Barr Virus Encoded lncRNAs Control the Viral Lytic Switch.bioRxiv : the preprint server for biology · 2025Article
- Pharmacomodulation of G-quadruplexes in long non-coding RNAs dysregulated in colorectal cancer.BMC biology · 2025Article
- RNA G-quadruplex structure targeting and imaging: recent advances and future directions.RNA (New York, N.Y.) · 2025Review
- Putative G‑Quadruplex Structures in Dysregulated Long Non-coding RNA of Ovarian Cancer and Their Binding Interactions with Human Serum Albumin.ACS omega · 2025Article
- Unraveling the Molecular Basis for G-Quadruplex-Binders to ALS/FTD-Associated G4C2 Repeats of the C9orf72 Gene.Chembiochem : a European journal of chemical biology · 2025Article
- G-Quadruplex Structures Formed by Human Telomere andInternational journal of molecular sciences · 2025Review
- Small molecules reveal differential shifts in stability and protein binding for G-quadruplex RNA.bioRxiv : the preprint server for biology · 2025Article
- Therapeutic targeting of RNA for neurological and neuromuscular disease.Genes & development · 2024Review
- 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
- Crystal structure of a tetrameric RNA G-quadruplex formed by hexanucleotide repeat expansions of C9orf72 in ALS/FTD.Nucleic acids research · 2024Article
- CGG repeats in the human FMR1 gene regulate mRNA localization and cellular stress in developing neurons.Cell reports · 2024Article
- Ribosomal quality control factors inhibit repeat-associated non-AUG translation from GC-rich repeats.Nucleic acids research · 2024Article
- Current potential therapeutics of amyotrophic lateral sclerosis.Frontiers in neurology · 2024Review
- A comparison study of pathological features and drug efficacy between Drosophila models of C9orf72 ALS/FTD.Molecules and cells · 2024Article
- Role of C9orf72 hexanucleotide repeat expansions in ALS/FTD pathogenesis.Frontiers in molecular neuroscience · 2024Review
- Translation Fidelity and Respiration Deficits in CLPP-Deficient Tissues: Mechanistic Insights from Mitochondrial Complexome Profiling.International journal of molecular sciences · 2023Article
46 more citing papers are in PubMed but not listed here.
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4 authors at 3 institutions in 2 countries.
Funding
Abstract
Certain DNA and RNA sequences can form G-quadruplexes, which can affect genetic instability, promoter activity, RNA splicing, RNA stability, and neurite mRNA localization. Amyotrophic lateral sclerosis and frontotemporal dementia can be caused by expansion of a (GGGGCC)n repeat in the C9orf72 gene. Mutant r(GGGGCC)n- and r(GGCCCC)n-containing transcripts aggregate in nuclear foci, possibly sequestering repeat-binding proteins such as ASF/SF2 and hnRNPA1, suggesting a toxic RNA pathogenesis, as occurs in myotonic dystrophy. Furthermore, the C9orf72 repeat RNA was recently demonstrated to undergo the noncanonical repeat-associated non-AUG translation (RAN translation) into pathologic dipeptide repeats in patient brains, a process that is thought to depend upon RNA structure. We previously demonstrated that the r(GGGGCC)n RNA forms repeat tract length-dependent G-quadruplex structures that bind the ASF/SF2 protein. Here we show that the cationic porphyrin (5,10,15,20-tetra(N-methyl-4-pyridyl) porphyrin (TMPyP4)), which can bind some G-quadruplex-forming sequences, can bind and distort the G-quadruplex formed by r(GGGGCC)8, and this ablates the interaction of either hnRNPA1 or ASF/SF2 with the repeat. These findings provide proof of concept that nucleic acid binding small molecules, such as TMPyP4, can distort the secondary structure of the C9orf72 repeat, which may beneficially disrupt protein interactions, which may ablate either protein sequestration and/or RAN translation into potentially toxic dipeptides. Disruption of secondary structure formation of the C9orf72 RNA repeats may be a viable therapeutic avenue, as well as a means to test the role of RNA structure upon RAN translation.
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