TY - JOUR A1 - Müller, Diana A1 - Bessi, Irene A1 - Richter, Christian A1 - Schwalbe, Harald T1 - The Folding Landscapes of Human Telomeric RNA and DNA G‐Quadruplexes are Markedly Different JF - Angewandte Chemie International Edition N2 - We investigated the folding kinetics of G‐quadruplex (G4) structures by comparing the K\(^{+}\)‐induced folding of an RNA G4 derived from the human telomeric repeat‐containing RNA (TERRA25) with a sequence homologous DNA G4 (wtTel25) using CD spectroscopy and real‐time NMR spectroscopy. While DNA G4 folding is biphasic, reveals kinetic partitioning and involves kinetically favoured off‐pathway intermediates, RNA G4 folding is faster and monophasic. The differences in kinetics are correlated to the differences in the folded conformations of RNA vs. DNA G4s, in particular with regard to the conformation around the glycosidic torsion angle χ that uniformly adopts anti conformations for RNA G4s and both, syn and anti conformation for DNA G4s. Modified DNA G4s with \(^{19}\)F bound to C2′ in arabino configuration adopt exclusively anti conformations for χ. These fluoro‐modified DNA (antiTel25) reveal faster folding kinetics and monomorphic conformations similar to RNA G4s, suggesting the correlation between folding kinetics and pathways with differences in χ angle preferences in DNA and RNA, respectively. KW - folding landscapes KW - G-quadruplexes KW - kinetics KW - real-time NMR spectroscopy KW - TERRA RNA Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238917 VL - 60 IS - 19 SP - 10895 EP - 10901 ER - TY - JOUR A1 - Binas, Oliver A1 - Bessi, Irene A1 - Schwalbe, Harald T1 - Structure Validation of G‐Rich RNAs in Noncoding Regions of the Human Genome JF - ChemBioChem N2 - We present the rapid biophysical characterization of six previously reported putative G‐quadruplex‐forming RNAs from the 5′‐untranslated region (5′‐UTR) of silvestrol‐sensitive transcripts for investigation of their secondary structures. By NMR and CD spectroscopic analysis, we found that only a single sequence—[AGG]\(_{2}\)[CGG]\(_{2}\)C—folds into a single well‐defined G‐quadruplex structure. Sequences with longer poly‐G strands form unspecific aggregates, whereas CGG‐repeat‐containing sequences exhibit a temperature‐dependent equilibrium between a hairpin and a G‐quadruplex structure. The applied experimental strategy is fast and provides robust readout for G‐quadruplex‐forming capacities of RNA oligomers. KW - biophysical investigation KW - circular dichroism KW - G-quadruplexes KW - NMR spectroscopy KW - RNA Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214892 VL - 21 IS - 11 SP - 1656 EP - 1663 ER -