ArticleNucleic acids research2025
G-quadruplex topologies determine the functional outcome of guanine-rich bioactive oligonucleotides.
Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- A water-soluble pyrene-based diimidazolium molecular probe enabling chirality and fluorescence dual-response toward G-quadruplexes.Chemical science · 2026Article
- Precise discrimination of G-quadruplex conformation by chiral nanoassembly with photo-reversibility.Nature communications · 2026Article
- Targeting G-Rich lncRNA and Its Structural Polymorphism With Selective G-Quadruplex Ligands: An NMR Study.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Age-associated G-quadruplex accumulation and DDX5 loss shape chromatin landscapes in human astrocytes.Research square · 2025Article
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Abstract
Guanine-rich nucleic acid sequences can exert sequence- and/or structure-specific activities to influence biological and pathobiological cellular processes. As such, it has been reported that different G-rich oligonucleotides (both DNA and RNA) can have cytotoxic as well as cytoprotective effects on the cells. However, the mechanisms of such a biological outcome are unclear. Here, we report that G-rich DNA oligonucleotides (ODNs) that can form four-stranded secondary structures called G-quadruplexes (G4s) have a topology-dependent biological outcome. Using different biochemical, biophysical, and cellular approaches, we demonstrate that only the parallel topology G4-forming ODNs can repress eukaryotic messenger RNA (mRNA) translation by directly interacting with eukaryotic translation initiation protein 1 (EIF4G1), while the anti-parallel topology G4s do not have inhibitory effect on mRNA translation. These results directly connect the G4 topological differences within ODNs to differential functional impacts in mRNA translation intrans. Our study provides the foundation for the rational design of G-rich oligonucleotides for a desired therapeutic outcome.
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