ArticleNucleic acids research2021
Cyclic mismatch binding ligands interact with disease-associated CGG trinucleotide repeats in RNA and suppress their translation.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- The role of FMR1 mRNA structure on the efficiency of non-canonical translation of toxic polyglycine protein.Nucleic acids research · 2026Article
- MBNL proteins in health, disease, and therapeutic applications.Nucleic acids research · 2026Review
- IGF2BPs directly regulate the noncanonical translation of toxic proteins from mutant FMR1 mRNA containing expanded CGG repeats.Nature communications · 2025Article
- High-Sensitivity Fluorescence-Based Detection of Reverse Transcriptase Read-Through of GC-Rich Short Tandem Repeat RNA.Analytical chemistry · 2025Article
- Advances on the Mechanisms and Therapeutic Strategies in Non-coding CGG Repeat Expansion Diseases.Molecular neurobiology · 2024Review
- Heterobifunctional small molecules to modulate RNA function.Trends in pharmacological sciences · 2024Review
- Small molecule approaches to targeting RNA.Nature reviews. Chemistry · 2024Review
- Review
- CGG repeats trigger translational frameshifts that generate aggregation-prone chimeric proteins.Nucleic acids research · 2022Article
- HT-SELEX-based identification of binding pre-miRNA hairpin-motif for small molecules.Molecular therapy. Nucleic acids · 2022Article
- Trinucleotide CGG Repeat Diseases: An Expanding Field of Polyglycine Proteins?Frontiers in genetics · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by a limited expansion of CGG repeats in the FMR1 gene. Degeneration of neurons in FXTAS cell models can be triggered by accumulation of polyglycine protein (FMRpolyG), a by-product of translation initiated upstream to the repeats. Specific aims of our work included testing if naphthyridine-based molecules could (i) block FMRpolyG synthesis by binding to CGG repeats in RNA, (ii) reverse pathological alterations in affected cells and (iii) preserve the content of FMRP, translated from the same FMR1 mRNA. We demonstrate that cyclic mismatch binding ligand CMBL4c binds to RNA structure formed by CGG repeats and attenuates translation of FMRpolyG and formation of nuclear inclusions in cells transfected with vectors expressing RNA with expanded CGG repeats. Moreover, our results indicate that CMBL4c delivery can reduce FMRpolyG-mediated cytotoxicity and apoptosis. Importantly, its therapeutic potential is also observed once the inclusions are already formed. We also show that CMBL4c-driven FMRpolyG loss is accompanied by partial FMRP reduction. As complete loss of FMRP induces FXS in children, future experiments should aim at evaluation of CMBL4c therapeutic intervention in differentiated tissues, in which FMRpolyG translation inhibition might outweigh adverse effects related to FMRP depletion.
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