More than proton detection - new avenues for NMR spectroscopy of RNA

  • Ribonucleic acid oligonucleotides (RNAs) play pivotal roles in cellular function (riboswitches), chemical biology applications (SELEX-derived aptamers), cell biology and biomedical applications (transcriptomics). Furthermore, a growing number of RNA forms (long non-coding RNAs, circular RNAs) but also RNA modifications are identified, showing the ever increasing functional diversity of RNAs. To describe and understand this functional diversity, structural studies of RNA are increasingly important. However, they are often more challenging than protein structural studies as RNAs are substantially more dynamic and their function is often linked to their structural transitions between alternative conformations. NMR is a prime technique to characterize these structural dynamics with atomic resolution. To extend the NMR size limitation and to characterize large RNAs and their complexes above 200 nucleotides, new NMR techniques have been developed. This Minireview reports on the development of NMR methods that utilize detection on low-γ nuclei (heteronuclei like 13C or 15N with lower gyromagnetic ratio than 1H) to obtain unique structural and dynamic information for large RNA molecules in solution. Experiments involve through-bond correlations of nucleobases and the phosphodiester backbone of RNA for chemical shift assignment and make information on hydrogen bonding uniquely accessible. Previously unobservable NMR resonances of amino groups in RNA nucleobases are now detected in experiments involving conformational exchange-resistant double-quantum 1H coherences, detected by 13C NMR spectroscopy. Furthermore, 13C and 15N chemical shifts provide valuable information on conformations. All the covered aspects point to the advantages of low-γ nuclei detection experiments in RNA.

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Author:Robbin Schnieders, Sara Keyhani, Harald SchwalbeORCiDGND, Boris FürtigORCiDGND
Parent Title (English):Chemistry
Place of publication:Weinheim
Document Type:Article
Date of Publication (online):2019/08/27
Date of first Publication:2019/08/27
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/01/25
Tag:NMR; RNA therapy; carbon direct detection; heteronuclear detection; nitrogen direct detection
Page Number:12
First Page:102
Last Page:113
R.S. is a recipient of a stipend of the Fonds der Chemischen Industrie. S.K., H.S. and B.F. are supported by the DFG in graduate school CLIC (GRK 1986). H.S. and B.F. are supported by the DFG in the collaborative research center 902, Work at BMRZ is supported by the state of Hesse.
Institutes:Biochemie, Chemie und Pharmazie
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 54 Chemie / 540 Chemie und zugeordnete Wissenschaften
Licence (German):License LogoCreative Commons - Namensnennung 4.0