Structural and dynamic effects of pseudouridine modifications on noncanonical interactions in RNA

0574517 - BFÚ 2024 RIV US eng J - Journal Article
Voegele, J. - Duchardt-Ferner, E. - Kruse, Holger - Zhang, Zhengyue - Šponer, Jiří - Krepl, Miroslav - Woehnert, J.
Structural and dynamic effects of pseudouridine modifications on noncanonical interactions in RNA.
RNA. Roč. 29, č. 6 (2023), s. 790-807. ISSN 1355-8382. E-ISSN 1469-9001
R&D Projects: GA ČR(CZ) GA23-05639S
Institutional support: RVO:68081707
Keywords : pseudouridine * RNA structure * U-turn * U base pair * nmr * MD simulations
OECD category: Biochemistry and molecular biology
Impact factor: 4.5, year: 2022
Method of publishing: Limited access
https://rnajournal.cshlp.org/content/29/6/790

Pseudouridine is the most frequently naturally occurring RNA modification, found in all classes of biologically functional RNAs. Compared to uridine, pseudouridine contains an additional hydrogen bond donor group and is therefore widely regarded as a structure stabilizing modification. However, the effects of pseudouridine modifications on the structure and dynamics of RNAs have so far only been investigated in a limited number of different structural contexts. Here, we introduced pseudouridine modifications into the U-turn motif and the adjacent U:U closing base pair of the neomycin-sensing riboswitch (NSR)-an extensively characterized model system for RNA structure, ligand binding, and dynamics. We show that the effects of replacing specific uridines with pseudouridines on RNA dynamics crucially depend on the exact location of the replacement site and can range from destabilizing to locally or even globally stabilizing. By using a combination of NMR spectroscopy, MD simulations and QM calculations, we rationalize the observed effects on a structural and dynamical level. Our results will help to better understand and predict the consequences of pseudouridine modifications on the structure and function of biologically important RNAs.
Permanent Link: https://hdl.handle.net/11104/0350076