The folding landscapes of human telomeric RNA and DNA G-quadruplexes are markedly different

  • 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 19F 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.

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Author:Diana Müller, Irene BessiORCiDGND, Christian RichterORCiDGND, Harald SchwalbeORCiDGND
Parent Title (English):Angewandte Chemie
Place of publication:Weinheim
Document Type:Article
Date of Publication (online):2021/02/04
Date of first Publication:2021/02/04
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/08/25
Tag:G-quadruplexes; TERRA RNA; folding landscapes; kinetics; real-time NMR spectroscopy
Page Number:7
First Page:10895
Last Page:10901
Work at BMRZ is supported by the state of Hesse, D.M. has been supported by EU-funded iNEXT-discovery. H.S. and D.M. have been supported by DFG-Normalverfahren and by DFG collaborative research center 902. Open access funding enabled and organized by Projekt DEAL.
Institutes:Biochemie, Chemie und Pharmazie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Licence (German):License LogoCreative Commons - Namensnennung 4.0