9WHV

Cross-Stacking-Stabilized Intra-Locked RNA G-Quadruplex

Summary for 9WHV

• Entry DOI: 10.2210/pdb9whv/pdb
• Descriptor: RNA (5'-R(*GP*UP*UP*AP*GP*GP*GP*UP*UP*A)-3') (1 entity in total)
• Functional Keywords: g-quadruplex, 16-layers, interlocked, high serum stability, rna
• Biological source: Homo sapiens
• Total number of polymer chains: 8
• Total formula weight: 25751.52

Authors

Xiao, C.D.,Wang, L.W.,Wang, S.Y.,Xu, Y. (deposition date: 2025-08-27, release date: 2025-10-15, Last modification date: 2026-06-24)

Primary citation

Song, S.S.,Yang, L.,Wang, L.W.,Tian, R.Q.,Wang, S.Y.,Jia, M.H.,Xu, Y.,Zhong, M.Q.,Liang, X.G.,Hu, K.L.,Luo, H.,Chen, Y.,Hu, X.X.,Shen, X.C.,Xiao, C.D.
An intra-locked RNA G-quadruplex topology confers enhanced nuclease resistance and cancer cell targeting.
Int.J.Biol.Macromol., 367:152564-152564, 2026

PubMed Abstract: Nucleic acid aptamers often suffer from poor serum nuclease resistance, which limits their translational applications. Here, we present Apt-10-2, a natural 10-nt RNA aptamer that forms a highly stable G-quadruplex (Tm > 90 °C) with prolonged serum persistence (>96 h), while maintaining nanomolar affinity for nucleolin (NCL). Functionally, Apt-10-2 distinguishes cancer cells from normal cells in vitro and demonstrates specific tumor accumulation (>8 h) in vivo. To investigate the molecular basis of its stability, we performed NMR-based structural analysis and proposed a restraint-supported structural model of Apt-10-2, suggesting a unique interlocked topology in which two subunits co-assemble into a 16-layered framework composed of G-, U-, and A-tetrad-like interactions.. The proposed structural model features an intra-locked domain stabilized by cross-stacking interactions between the G1-U2-U3 tetrads, which are critical for maintaining the aptamer's stability. Disruption of this domain significantly impairs the overall structure. Our findings provide a structural framework for understanding the prolonged stability of RNA G-quadruplexes, and highlight the potential of Apt-10-2 as a naturally stable, high-affinity aptamer scaffold for cancer-targeting applications, without the need for extensive chemical modifications.

PubMed: 42142778
DOI: 10.1016/j.ijbiomac.2026.152564

Experimental method

SOLUTION NMR