@misc{10481/103887,
year = {2025},
month = {3},
url = {https://hdl.handle.net/10481/103887},
abstract = {50 untranslated regions (UTRs) of mRNA commonly feature G-quadruplexes (G4s), crucial for translational
regulation and promising as drug targets to modulate gene expression. While NMR spectroscopy is wellsuited
for studying these motifs' structure and dynamics, their guanine-rich nature complicates
resonance assignment due to high signal overlap. Exploiting the inherent rigidity of G4 cores, we
developed a universally applicable assignment strategy for uniformly isotopically enriched G4 structures,
relying solely on through-bond correlations to establish the G-tetrads. Applying this approach, we
resolved the solution structures of two triple mutants of the RNA G4 in the 50 UTR of the human BCL2
proto-oncogene, one of the first natural monomolecular RNA G4 structures available to date.
Comparative analysis with other RNA and DNA G4s reveals their notably compact and well-defined
cores. Moreover, the sugar pucker geometries of the tetrad guanines are far less stringent than
previously assumed, adeptly accommodating specific structural features. This contrasts with the
canonical base pairing in RNA and DNA, in which the sugar pucker dictates the type of the doublehelical
structure. The strategy presented provides a direct path to uncovering G4 structural intricacies,
advancing our grasp of their biological roles, and paving the way for RNA-targeted therapeutics.},
organization = {Swiss National Science Foundation (165868)},
organization = {Candoc Grant of UZH (FK-14-100, FK- 15-096, FK-23-097)},
organization = {China Scholarship Council (No. 201506190127)},
organization = {UZH core},
publisher = {Royal Society of Chemistry},
title = {Elucidating the solution structure of the monomolecular BCL2 RNA G-quadruplex: a new robust NMR assignment approach},
doi = {10.1039/d5sc01416f},
author = {Wang, Zenghui and Ferreira Rodrigues, Carla and Jurt, Simon and Domínguez Martín, Alicia and Johannsen, Silke and Sigel, Roland K. O.},
}