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Structural and dynamic effects of pseudouridine modifications on noncanonical interactions in RNA
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SYSNO ASEP 0574517 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Structural and dynamic effects of pseudouridine modifications on noncanonical interactions in RNA Author(s) Voegele, J. (DE)
Duchardt-Ferner, E. (DE)
Kruse, Holger (BFU-R) ORCID
Zhang, Zhengyue (BFU-R)
Šponer, Jiří (BFU-R) RID, ORCID
Krepl, Miroslav (BFU-R) ORCID
Woehnert, J. (DE)Number of authors 7 Source Title RNA. - : Cold Spring Harbor Laboratory Press - ISSN 1355-8382
Roč. 29, č. 6 (2023), s. 790-807Number of pages 18 s. Publication form Print - P Language eng - English Country US - United States Keywords pseudouridine ; RNA structure ; U-turn ; U base pair ; nmr ; MD simulations Subject RIV CE - Biochemistry OECD category Biochemistry and molecular biology R&D Projects GA23-05639S GA ČR - Czech Science Foundation (CSF) Method of publishing Limited access Institutional support BFU-R - RVO:68081707 UT WOS 000989437200007 EID SCOPUS 85159738407 DOI 10.1261/rna.079506.122 Annotation 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. Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2024 Electronic address https://rnajournal.cshlp.org/content/29/6/790
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