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Structural and dynamic effects of pseudouridine modifications on noncanonical interactions in RNA
J. Vögele, E. Duchardt-Ferner, H. Kruse, Z. Zhang, J. Sponer, M. Krepl, J. Wöhnert
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 1995 to 6 months ago
PubMed Central
from 1995 to 1 year ago
Europe PubMed Central
from 1995 to 1 year ago
Open Access Digital Library
from 1995-03-01
- MeSH
- Nucleic Acid Conformation MeSH
- Base Pairing MeSH
- Pseudouridine * genetics MeSH
- RNA * genetics chemistry MeSH
- Uridine MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
CEITEC Central European Institute of Technology Masaryk University 625 00 Brno Czech Republic
Institute of Biophysics of the Czech Academy of Sciences 612 65 Brno Czech Republic
References provided by Crossref.org
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