Stabilization of RNA stacking by pseudouridine
Open accessAbstract
The effect of the modified nucleoside pseudouridine (psi) on RNA structure was compared with uridine. The extent of base stacking in model RNA oligonucleotides was measured by 1H NMR, UV, and CD spectroscopy. The UV and CD results indicate that the model single-stranded oligoribonucleotides AAUA and AA psi A form stacked structures in solution and the CD results for AA psi A are consistent with a general A-form helical conformation. The AA psi A oligomer exhibits a greater degree of UV hypochromicity over the temperature range 5-55 degrees C, consistent with a better stacked, more A-form structure compared with AAUA. The extent of stacking for each nucleotide residue was inferred from the percent 3'-endo sugar conformation as indicated by the H1'-H2' NMR scalar coupling. This indirect indication of stacking was confirmed by sequential NOE experiments. NMR measurements as a function of temperature indicate that pseudouridine forms a more stable base stacking arrangement than uridine, an effect that is propagated throughout the helix to stabilize stacking of neighboring purine nucleosides. The N1-H imino proton in AA psi A exchanges slowly with solvent, suggesting a role for the extra imino proton in stabilizing the conformation of pseudouridine. These results show that the conformational stabilization is an intrinsic property of pseudouridine occurring at the nucleotide level. The characteristics of pseudouridine in these models are consistent with earlier studies on intact rRNA, indicating that pseudouridine probably performs the same stabilizing function in most structural contexts.
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Incorporation of ψ enhances base-stacking interactions, which may lead to structural alterations.
“Incorporation of ψ has been shown to enhance base-stacking interactions, which may lead to structural alterations (Davis 1995)”
From RNA Circularization Diminishes Immunogenicity and Can Extend Translation Duration In Vivo (2019) · cites this paper as Davis 1995
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“Incorporation of ψ has been shown to enhance base-stacking interactions, which may lead to structural alterations (Davis 1995); however, it is possible that other nucleoside modifications may be more compatible with ribozyme and IRES structures and allow for the study of modified circRNA stability…”
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“In contrast, pseudouridine (Y) promotes base-stacking and stabilizes RNA duplexes, explaining why it is not as efficient at evading TLR 3 recognition (14, 51).”
BackgroundRibosomal flavours: An acquired taste for specific mRNAs?
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- Authors
- Davis, D. R.
- Affiliations
- University of Utah (US)
- Corresponding author
- Davis, Darrell R.
- Venue
- Nucleic Acids Research
- Publisher
- Oxford University Press (OUP)
- Published
- 1995
- Volume
- 23
- Issue
- 24
- Pages
- 5020-5026
- ISSN
- 0305-1048 (ISSN-L)
- 1362-4962
- PMC
- PMC307508
- OpenAlex
- W2014056463
- Cited by
- 399
- References
- 29
- Citations by year
- 2026: 22 · 2025: 26 · 2024: 35 · 2023: 32 · 2022: 19 · 2021: 29 · 2020: 16 · 2019: 17 · 2018: 15 · 2017: 15 · 2016: 23 · 2015: 16 · 2014: 23 · 2013: 11 · 2012: 5
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nucleic Acids Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (9317196)
- National Institutes of Health (1s10rr006262-01)
- National Cancer Institute (CA42014, P30CA042014)
- National Center for Research Resources (RR 06262)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Keywords
- pseudouridine, A-form helix, uridine, modified nucleosides, imino proton exchange
- MeSH terms
- Magnetic Resonance Spectroscopy, Nucleic Acid Conformation, Pseudouridine, RNA, Uridine, Molecular Structure
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