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Cited by 264RNA and protein synthesis mechanismsDNA and Nucleic Acid ChemistryRNA modifications and cancer

The contribution of pseudouridine to stabilities and structure of RNAs

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Kierzek, Elzbieta, Malgowska, Magdalena, Lisowiec, Jolanta, Turner, Douglas H., Gdaniec, Zofia, Kierzek, Ryszard·2014·Nucleic Acids Research
DOI 10.1093/nar/gkt1330PMC PMC3950712
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Abstract

Thermodynamic data are reported revealing that pseudouridine (Ψ) can stabilize RNA duplexes when replacing U and forming Ψ-A, Ψ-G, Ψ-U and Ψ-C pairs. Stabilization is dependent on type of base pair, position of Ψ within the RNA duplex, and type and orientation of adjacent Watson–Crick pairs. NMR spectra demonstrate that for internal Ψ-A, Ψ-G and Ψ-U pairs, the N3 imino proton is hydrogen bonded to the opposite strand nucleotide and the N1 imino proton may also be hydrogen bonded. CD spectra show that general A-helix structure is preserved, but there is some shifting of peaks and changing of intensities. Ψ has two hydrogen donors (N1 and N3 imino protons) and two hydrogen bond acceptors because the glycosidic bond is C-C rather than C-N as in uridine. This greater structural potential may allow Ψ to behave as a kind of structurally driven universal base because it can enhance stability relative to U when paired with A, G, U or C inside a double helix. These structural and thermodynamic properties may contribute to the biological functions of Ψ.

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  • The improvement in prediction accuracy from training on modified RNAs is likely due to the model learning the impact of Ψ and m1Ψ on the formation of secondary structure.

    “This is likely due to the model learning the impact of Ψ and m1Ψ on the formation of secondary structure33.”

    From Human 5′ UTR design and variant effect prediction from a massively parallel translation assay (2019) · cites this paper as [33]

    The Results section reports that replacing U with Ψ usually increases RNA-duplex stability, supporting the premise that Ψ can affect RNA structure. The paper does not establish an effect of m1Ψ or examine whether a model learned either modification’s effects, so it cannot substantiate the proposed explanation for improved prediction accuracy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Ψ is more promiscuous in base-pairing than U and can pair with both A and G and, to a lesser extent, with C and U, so stop codons become more prone to misreading by tRNAs.

    “As Ψ is more promiscuous in base-pairing than U and can pair with both A and G and, to a less extent, with C and U [16], stop codons become more prone to misreading by tRNAs [17].”

    From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [16]

    The Discussion reports Ψ-A, Ψ-G and Ψ-U hydrogen bonding and generally greater stability when Ψ replaces U in mispairs. But it says Ψ and U hydrogen-bond to those bases in similar ways, and finds no NMR evidence of hydrogen bonding in Ψ-C, so the claimed greater breadth of base-pairing is not established. The stop-codon clause is attached to a different citation and is not judged here. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Ψ wobbles more in base-pairing than U and can pair not only with A and G, but also, to a lesser extent, with C and U.

    “However, Ψ wobbles more in base-pairing than U and can pair not only with A and G, but also, to a lesser extent, with C and U [16].”

    From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [16]

  • G/Ψ base pairs are expected to be stronger than G/U base pairs.

    “G/Ψ base pairs are expected to be stronger than G/U base pairs [16].”

    From Detailed Dissection and Critical Evaluation of the Pfizer/BioNTech and Moderna mRNA Vaccines (2021) · cites this paper as [16]

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Authors
Kierzek, E., Malgowska, M., Lisowiec, J., Turner, D. H., Gdaniec, Z., & Kierzek, R.
Affiliations
Institute of Bioorganic Chemistry, Polish Academy of Sciences (PL)
Corresponding author
Kierzek, Ryszard
ORCID
Venue
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Published
2013-12-24
Volume
42
Issue
5
Pages
3492-3501
ISSN
  • 0305-1048 (ISSN-L)
  • 1362-4962
DOI
10.1093/nar/gkt1330
PMC
PMC3950712
OpenAlex
W2121138963
Cited by
264
References
0
Citations by year
2026: 33 · 2025: 37 · 2024: 35 · 2023: 27 · 2022: 21 · 2021: 26 · 2020: 16 · 2019: 12 · 2018: 16 · 2017: 13 · 2016: 13 · 2015: 8 · 2014: 7
FWCI
3.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Nucleic Acids Research (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (GM 22939, R01GM022939)
  • Fogarty International Center (R03TW008739)
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, RNA duplex stability, RNA base pairing, hydrogen bonding, thermodynamic stability, universal base, RNA structure
MeSH terms
Hydrogen Bonding, Pseudouridine, RNA, Double-Stranded, Thermodynamics, Base Pairing, RNA Stability

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