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Integrating cryo-OrbiSIMS with computational modelling and metadynamics simulations enhances RNA structure prediction at atomic resolution

Author

Listed:
  • Shannon Ward

    (University of Nottingham
    University of Nottingham)

  • Alex Childs

    (University of Nottingham
    University of Nottingham)

  • Ceri Staley

    (University of Nottingham)

  • Christopher Waugh

    (University of Nottingham
    University of Nottingham
    RHy-X Limited)

  • Julie A. Watts

    (University of Nottingham)

  • Anna M. Kotowska

    (University of Nottingham)

  • Rahul Bhosale

    (University of Nottingham)

  • Aditi N. Borkar

    (University of Nottingham
    University of Nottingham
    RHy-X Limited)

Abstract

The 3D architecture of RNAs governs their molecular interactions, chemical reactions, and biological functions. However, a large number of RNAs and their protein complexes remain poorly understood due to the limitations of conventional structural biology techniques in deciphering their complex structures and dynamic interactions. To address this limitation, we have benchmarked an integrated approach that combines cryogenic OrbiSIMS, a state-of-the-art solid-state mass spectrometry technique, with computational methods for modelling RNA structures at atomic resolution with enhanced precision. Furthermore, using 7SK RNP as a test case, we have successfully determined the full 3D structure of a native RNA in its apo, native and disease-remodelled states, which offers insights into the structural interactions and plasticity of the 7SK complex within these states. Overall, our study establishes cryo-OrbiSIMS as a valuable tool in the field of RNA structural biology as it enables the study of challenging, native RNA systems.

Suggested Citation

  • Shannon Ward & Alex Childs & Ceri Staley & Christopher Waugh & Julie A. Watts & Anna M. Kotowska & Rahul Bhosale & Aditi N. Borkar, 2024. "Integrating cryo-OrbiSIMS with computational modelling and metadynamics simulations enhances RNA structure prediction at atomic resolution," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48694-3
    DOI: 10.1038/s41467-024-48694-3
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    References listed on IDEAS

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    1. Vincent V. Pham & Carolina Salguero & Shamsun Nahar Khan & Jennifer L. Meagher & W. Clay Brown & Nicolas Humbert & Hugues Rocquigny & Janet L. Smith & Victoria M. D’Souza, 2018. "HIV-1 Tat interactions with cellular 7SK and viral TAR RNAs identifies dual structural mimicry," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    2. Zhiyuan Yang & Qingwei Zhu & Kunxin Luo & Qiang Zhou, 2001. "The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription," Nature, Nature, vol. 414(6861), pages 317-322, November.
    3. Michael Graf & Paul Huter & Cristina Maracci & Miroslav Peterek & Marina V. Rodnina & Daniel N. Wilson, 2018. "Visualization of translation termination intermediates trapped by the Apidaecin 137 peptide during RF3-mediated recycling of RF1," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
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