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Shedding light on the base-pair opening dynamics of nucleic acids in living human cells

Author

Listed:
  • Yudai Yamaoki

    (Kyoto University
    Kyoto University
    Kyoto University)

  • Takashi Nagata

    (Kyoto University
    Kyoto University
    Kyoto University)

  • Keiko Kondo

    (Kyoto University
    Kyoto University
    Kyoto University)

  • Tomoki Sakamoto

    (Kyoto University)

  • Shohei Takami

    (Kyoto University)

  • Masato Katahira

    (Kyoto University
    Kyoto University
    Kyoto University
    Kyoto University)

Abstract

Base-pair opening is a fundamental property of nucleic acids that plays important roles in biological functions. However, studying the base-pair opening dynamics inside living cells has remained challenging. Here, to determine the base-pair opening kinetics inside living human cells, the exchange rate constant ( $${k}_{{{{{{\rm{ex}}}}}}}$$ k ex ) of the imino proton with the proton of solvent water involved in hairpin and G-quadruplex (GQ) structures is determined by the in-cell NMR technique. It is deduced on determination of $${k}_{{{{{{\rm{ex}}}}}}}$$ k ex values that at least some G-C base pairs of the hairpin structure and all G-G base-pairs of the GQ structure open more frequently in living human cells than in vitro. It is suggested that interactions with endogenous proteins could be responsible for the increase in frequency of base-pair opening. Our studies demonstrate a difference in dynamics of nucleic acids between in-cell and in vitro conditions.

Suggested Citation

  • Yudai Yamaoki & Takashi Nagata & Keiko Kondo & Tomoki Sakamoto & Shohei Takami & Masato Katahira, 2022. "Shedding light on the base-pair opening dynamics of nucleic acids in living human cells," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34822-4
    DOI: 10.1038/s41467-022-34822-4
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    1. Tomonori Shibata & Konami Nagano & Morio Ueyama & Kensuke Ninomiya & Tetsuro Hirose & Yoshitaka Nagai & Kinya Ishikawa & Gota Kawai & Kazuhiko Nakatani, 2021. "Small molecule targeting r(UGGAA)n disrupts RNA foci and alleviates disease phenotype in Drosophila model," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    2. John A. Howe & Hao Wang & Thierry O. Fischmann & Carl J. Balibar & Li Xiao & Andrew M. Galgoci & Juliana C. Malinverni & Todd Mayhood & Artjohn Villafania & Ali Nahvi & Nicholas Murgolo & Christopher , 2015. "Selective small-molecule inhibition of an RNA structural element," Nature, Nature, vol. 526(7575), pages 672-677, October.
    3. Bei Liu & Honglue Shi & Atul Rangadurai & Felix Nussbaumer & Chia-Chieh Chu & Kevin Andreas Erharter & David A. Case & Christoph Kreutz & Hashim M. Al-Hashimi, 2021. "A quantitative model predicts how m6A reshapes the kinetic landscape of nucleic acid hybridization and conformational transitions," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
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