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

MD simulations NMR RNA structure U-turn U:U base pair pseudouridine

Journal

RNA (New York, N.Y.)
ISSN: 1469-9001
Titre abrégé: RNA
Pays: United States
ID NLM: 9509184

Informations de publication

Date de publication:
06 2023
Historique:
received: 03 11 2022
accepted: 10 02 2023
pmc-release: 01 06 2024
medline: 18 5 2023
pubmed: 4 3 2023
entrez: 3 3 2023
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 36868785
pii: rna.079506.122
doi: 10.1261/rna.079506.122
pmc: PMC10187676
doi:

Substances chimiques

RNA 63231-63-0
Pseudouridine 1445-07-4
Uridine WHI7HQ7H85

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

790-807

Informations de copyright

© 2023 Vögele et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

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Auteurs

Jennifer Vögele (J)

Institute of Molecular Biosciences and Center for Biomolecular Magnetic Resonance (BMRZ), Goethe-University Frankfurt, 60438 Frankfurt, Germany.

Elke Duchardt-Ferner (E)

Institute of Molecular Biosciences and Center for Biomolecular Magnetic Resonance (BMRZ), Goethe-University Frankfurt, 60438 Frankfurt, Germany.

Holger Kruse (H)

Institute of Biophysics of the Czech Academy of Sciences, 612 65 Brno, Czech Republic.

Zhengyue Zhang (Z)

Institute of Biophysics of the Czech Academy of Sciences, 612 65 Brno, Czech Republic.
CEITEC-Central European Institute of Technology, Masaryk University, 625 00 Brno, Czech Republic.
National Centre for Biomolecular Research, Faculty of Science, Masaryk University, 625 00 Brno, Czech Republic.

Jiri Sponer (J)

Institute of Biophysics of the Czech Academy of Sciences, 612 65 Brno, Czech Republic.

Miroslav Krepl (M)

Institute of Biophysics of the Czech Academy of Sciences, 612 65 Brno, Czech Republic krepl@seznam.cz woehnert@bio.uni-frankfurt.de.

Jens Wöhnert (J)

Institute of Molecular Biosciences and Center for Biomolecular Magnetic Resonance (BMRZ), Goethe-University Frankfurt, 60438 Frankfurt, Germany krepl@seznam.cz woehnert@bio.uni-frankfurt.de.

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Classifications MeSH