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Multiple Non-Canonical Base-Stacking Interactions as One of the Major Determinants of RNA Tertiary Structure Organization

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Abstract

Stacking interactions of heterocyclic bases of ribonucleotides are one of the most important factors in the organization of RNA secondary and tertiary structure. Most of these (canonical) interactions are formed between adjacent residues in RNA polynucleotide chains. However, with the accumulation of data on the atomic tertiary structures of various RNAs and their complexes with proteins, it has become clear that nucleotide residues that are not adjacent in the polynucleotide chains and are sometimes separated in the RNA primary structure by tens or hundreds of nucleotides can interact via (non-canonical) base stacking. This paper presents an exhaustive database of such nonadjacent base-stacking elements (NA-BSEs) and their environment in the macromolecules of natural and synthetic RNAs. Analysis of these data showed that NA-BSE-forming nucleotides, on average, account for about a quarter of all nucleotides in a particular RNA and, therefore, should be considered as bona fide motifs of the RNA tertiary structure. We also classified NA-BSEs by their location in RNA macromolecules. It was shown that the structure-forming role of NA-BSEs involves compact folding of single-stranded RNA loops, transformation of double-stranded bulges into imperfect helices, and binding of RNA regions distant in the primary and secondary RNA structure.

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Abbreviations

BIE:

base-intercalated element

BWE:

base-wedged element

DC:

double-crossing

NA-BSE:

nonadjacent base-stacking element

RNase P:

ribonuclease P

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Acknowledgments

The authors thank the reviewers for their careful reading of the manuscript and constructive suggestions.

Funding

V.M. and A.B. thank Lomonosov Moscow State University and Ministry of Science and Higher Education of the Russian Federation for support (Agreement 1075-15-2021-1949 of 28.09.21).

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Authors and Affiliations

  1. Faculty of Chemistry, Lomonosov Moscow State University, 119991, Moscow, Russia

    Valeriy G. Metelev & Alexey A. Bogdanov

  2. Institute of Mathematical Problems of Biology, Keldysh Institute of Applied Mathematics, Russian Academy of Sciences, 142290, Pushchino, Moscow Region, Russia

    Eugene F. Baulin

  3. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992, Moscow, Russia

    Alexey A. Bogdanov

  4. Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry, 117997, Moscow, Russia

    Alexey A. Bogdanov

Authors
  1. Valeriy G. Metelev
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  2. Eugene F. Baulin
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  3. Alexey A. Bogdanov
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Contributions

E.B. performed computational work and conformational analysis. V.M. analyzed the data and prepared all figures. A.B. developed the project. All authors contributed to writing the manuscript.

Corresponding author

Correspondence to Alexey A. Bogdanov.

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The authors declare no conflict of interest. This article does not contain description of studies with the involvement of humans or animal subjects performed by any of the authors.

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Metelev, V.G., Baulin, E.F. & Bogdanov, A.A. Multiple Non-Canonical Base-Stacking Interactions as One of the Major Determinants of RNA Tertiary Structure Organization. Biochemistry Moscow 88, 792–800 (2023). https://doi.org/10.1134/S000629792306007X

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  • DOI: https://doi.org/10.1134/S000629792306007X

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