IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-44174-2.html
   My bibliography  Save this article

Monovalent metal ion binding promotes the first transesterification reaction in the spliceosome

Author

Listed:
  • Jana Aupič

    (National Research Council of Italy (CNR)—Materials Foundry (IOM) c/o International School for Advanced Studies (SISSA))

  • Jure Borišek

    (National Institute of Chemistry)

  • Sebastian M. Fica

    (University of Oxford)

  • Wojciech P. Galej

    (European Molecular Biology Laboratory)

  • Alessandra Magistrato

    (National Research Council of Italy (CNR)—Materials Foundry (IOM) c/o International School for Advanced Studies (SISSA))

Abstract

Cleavage and formation of phosphodiester bonds in nucleic acids is accomplished by large cellular machineries composed of both protein and RNA. Long thought to rely on a two-metal-ion mechanism for catalysis, structure comparisons revealed many contain highly spatially conserved second-shell monovalent cations, whose precise function remains elusive. A recent high-resolution structure of the spliceosome, essential for pre-mRNA splicing in eukaryotes, revealed a potassium ion in the active site. Here, we employ biased quantum mechanics/ molecular mechanics molecular dynamics to elucidate the function of this monovalent ion in splicing. We discover that the K+ ion regulates the kinetics and thermodynamics of the first splicing step by rigidifying the active site and stabilizing the substrate in the pre- and post-catalytic state via formation of key hydrogen bonds. Our work supports a direct role for the K+ ion during catalysis and provides a mechanistic hypothesis likely shared by other nucleic acid processing enzymes.

Suggested Citation

  • Jana Aupič & Jure Borišek & Sebastian M. Fica & Wojciech P. Galej & Alessandra Magistrato, 2023. "Monovalent metal ion binding promotes the first transesterification reaction in the spliceosome," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44174-2
    DOI: 10.1038/s41467-023-44174-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-44174-2
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-44174-2?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Alexey Rozov & Iskander Khusainov & Kamel El Omari & Ramona Duman & Vitaliy Mykhaylyk & Marat Yusupov & Eric Westhof & Armin Wagner & Gulnara Yusupova, 2019. "Importance of potassium ions for ribosome structure and function revealed by long-wavelength X-ray diffraction," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    2. Sebastian M. Fica & Nicole Tuttle & Thaddeus Novak & Nan-Sheng Li & Jun Lu & Prakash Koodathingal & Qing Dai & Jonathan P. Staley & Joseph A. Piccirilli, 2013. "RNA catalyses nuclear pre-mRNA splicing," Nature, Nature, vol. 503(7475), pages 229-234, November.
    3. Jacopo Manigrasso & Isabel Chillón & Vito Genna & Pietro Vidossich & Srinivas Somarowthu & Anna Marie Pyle & Marco De Vivo & Marco Marcia, 2020. "Visualizing group II intron dynamics between the first and second steps of splicing," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    4. Wojciech P. Galej & Max E. Wilkinson & Sebastian M. Fica & Chris Oubridge & Andrew J. Newman & Kiyoshi Nagai, 2016. "Cryo-EM structure of the spliceosome immediately after branching," Nature, Nature, vol. 537(7619), pages 197-201, September.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Michael F. Fuss & Jan-Philip Wieferig & Robin A. Corey & Yvonne Hellmich & Igor Tascón & Joana S. Sousa & Phillip J. Stansfeld & Janet Vonck & Inga Hänelt, 2023. "Cyclic di-AMP traps proton-coupled K+ transporters of the KUP family in an inward-occluded conformation," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Dylan Girodat & Hans-Joachim Wieden & Scott C. Blanchard & Karissa Y. Sanbonmatsu, 2023. "Geometric alignment of aminoacyl-tRNA relative to catalytic centers of the ribosome underpins accurate mRNA decoding," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Vivek Singh & Yuzuru Itoh & Samuel Del’Olio & Asem Hassan & Andreas Naschberger & Rasmus Kock Flygaard & Yuko Nobe & Keiichi Izumikawa & Shintaro Aibara & Juni Andréll & Paul C. Whitford & Antoni Barr, 2024. "Mitoribosome structure with cofactors and modifications reveals mechanism of ligand binding and interactions with L1 stalk," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    4. Xiechao Zhan & Yichen Lu & Yigong Shi, 2024. "Molecular basis for the activation of human spliceosome," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    5. K. Shanmugha Rajan & Hava Madmoni & Anat Bashan & Masato Taoka & Saurav Aryal & Yuko Nobe & Tirza Doniger & Beathrice Galili Kostin & Amit Blumberg & Smadar Cohen-Chalamish & Schraga Schwartz & Andre , 2023. "A single pseudouridine on rRNA regulates ribosome structure and function in the mammalian parasite Trypanosoma brucei," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Bangjun Zhou & Huihui Yu & Yong Xue & Mu Li & Chi Zhang & Bin Yu, 2024. "The spliceosome-associated protein CWC15 promotes miRNA biogenesis in Arabidopsis," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. Ahmed Moursy & Antoine Cléry & Stefan Gerhardy & Katharina M. Betz & Sanjana Rao & Jarosław Mazur & Sébastien Campagne & Irene Beusch & Malgorzata M. Duszczyk & Mark D. Robinson & Vikram Govind Panse , 2023. "RNA recognition by Npl3p reveals U2 snRNA-binding compatible with a chaperone role during splicing," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Seisuke Yamashita & Kozo Tomita, 2023. "Mechanism of U6 snRNA oligouridylation by human TUT1," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    9. Simon A. Fromm & Kate M. O’Connor & Michael Purdy & Pramod R. Bhatt & Gary Loughran & John F. Atkins & Ahmad Jomaa & Simone Mattei, 2023. "The translating bacterial ribosome at 1.55 Å resolution generated by cryo-EM imaging services," Nature Communications, Nature, vol. 14(1), pages 1-9, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-44174-2. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.