IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v16y2025i1d10.1038_s41467-025-62342-4.html
   My bibliography  Save this article

An RNA modification prevents extended codon-anticodon interactions from facilitating +1 frameshifting

Author

Listed:
  • Evelyn M. Kimbrough

    (Emory University)

  • Ha An Nguyen

    (Emory University)

  • Haixing Li

    (Columbia University
    City University of Hong Kong)

  • Jacob M. Mattingly

    (Emory University
    Emory University)

  • Nevette A. Bailey

    (Columbia University)

  • Wei Ning

    (Columbia University)

  • Howard Gamper

    (Thomas Jefferson University)

  • Ya-Ming Hou

    (Thomas Jefferson University)

  • Ruben L. Gonzalez

    (Columbia University)

  • Christine M. Dunham

    (Emory University)

Abstract

RNA post-transcriptional modifications act by stabilizing the functional conformations of RNA. While their role in messenger RNA (mRNA) decoding is well established, it is less clear how transfer RNA (tRNA) modifications outside the anticodon contribute to tRNA stability and accurate protein synthesis. Absence of such modifications causes translation errors, including mRNA frameshifting. By integrating single-molecule fluorescence resonance energy transfer and cryogenic electron microscopy, we demonstrate that the N1-methylguanosine (m1G) modification at position 37 of Escherichia coli tRNAProL is necessary and sufficient for modulating the conformational energy of this tRNA on the ribosome so as to suppress +1 frameshifting otherwise induced by this tRNA. Six structures of E. coli ribosomal complexes carrying tRNAProL lacking m1G37 show this tRNA forms four and even five codon-anticodon base pairs as it moves into the +1 frame, allowing direct visualization of the long-standing hypothesis that a four base pair codon-anticodon can form during +1 frameshifting.

Suggested Citation

  • Evelyn M. Kimbrough & Ha An Nguyen & Haixing Li & Jacob M. Mattingly & Nevette A. Bailey & Wei Ning & Howard Gamper & Ya-Ming Hou & Ruben L. Gonzalez & Christine M. Dunham, 2025. "An RNA modification prevents extended codon-anticodon interactions from facilitating +1 frameshifting," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62342-4
    DOI: 10.1038/s41467-025-62342-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-025-62342-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-025-62342-4?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. Suki Albers & Elizabeth C. Allen & Nikhil Bharti & Marcos Davyt & Disha Joshi & Carlos G. Perez-Garcia & Leonardo Santos & Rajesh Mukthavaram & Miguel Angel Delgado-Toscano & Brandon Molina & Kristen , 2023. "Engineered tRNAs suppress nonsense mutations in cells and in vivo," Nature, Nature, vol. 618(7966), pages 842-848, June.
    2. Howard B. Gamper & Isao Masuda & Milana Frenkel-Morgenstern & Ya-Ming Hou, 2015. "Maintenance of protein synthesis reading frame by EF-P and m1G37-tRNA," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    3. Howard Gamper & Haixing Li & Isao Masuda & D. Miklos Robkis & Thomas Christian & Adam B. Conn & Gregor Blaha & E. James Petersson & Ruben L. Gonzalez & Ya-Ming Hou, 2021. "Insights into genome recoding from the mechanism of a classic +1-frameshifting tRNA," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    4. Gabriel Demo & Howard B. Gamper & Anna B. Loveland & Isao Masuda & Christine E. Carbone & Egor Svidritskiy & Ya-Ming Hou & Andrei A. Korostelev, 2021. "Structural basis for +1 ribosomal frameshifting during EF-G-catalyzed translocation," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    5. 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.
    6. Zachary D. Aron & Atousa Mehrani & Eric D. Hoffer & Kristie L. Connolly & Pooja Srinivas & Matthew C. Torhan & John N. Alumasa & Mynthia Cabrera & Divya Hosangadi & Jay S. Barbor & Steven C. Cardinale, 2021. "trans-Translation inhibitors bind to a novel site on the ribosome and clear Neisseria gonorrhoeae in vivo," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    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. Yuko Nakano & Howard Gamper & Henri McGuigan & Sunita Maharjan & Jiatong Li & Zhiyi Sun & Erbay Yigit & Sebastian Grünberg & Keerthana Krishnan & Nan-Sheng Li & Joseph A. Piccirilli & Ralph Kleiner & , 2025. "Genome-wide profiling of tRNA modifications by Induro-tRNAseq reveals coordinated changes," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    2. Panagiotis Poulis & Anoshi Patel & Marina V. Rodnina & Sarah Adio, 2022. "Altered tRNA dynamics during translocation on slippery mRNA as determinant of spontaneous ribosome frameshifting," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Asuteka Nagao & Yui Nakanishi & Yutaro Yamaguchi & Yoshifumi Mishina & Minami Karoji & Takafumi Toya & Tomoya Fujita & Shintaro Iwasaki & Kenjyo Miyauchi & Yuriko Sakaguchi & Tsutomu Suzuki, 2023. "Quality control of protein synthesis in the early elongation stage," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Nikhil Bharti & Leonardo Santos & Marcos Davyt & Stine Behrmann & Marie Eichholtz & Alejandro Jimenez-Sanchez & Jeong S. Hong & Andras Rab & Eric J. Sorscher & Suki Albers & Zoya Ignatova, 2024. "Translation velocity determines the efficacy of engineered suppressor tRNAs on pathogenic nonsense mutations," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    5. Christine E. Carbone & Anna B. Loveland & Howard B. Gamper & Ya-Ming Hou & Gabriel Demo & Andrei A. Korostelev, 2021. "Time-resolved cryo-EM visualizes ribosomal translocation with EF-G and GTP," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    6. Caillan Crowe-McAuliffe & Victoriia Murina & Kathryn Jane Turnbull & Susanne Huch & Marje Kasari & Hiraku Takada & Lilit Nersisyan & Arnfinn Sundsfjord & Kristin Hegstad & Gemma C. Atkinson & Vicent P, 2022. "Structural basis for PoxtA-mediated resistance to phenicol and oxazolidinone antibiotics," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    7. Laura K. White & Aleksandar Radakovic & Marcin P. Sajek & Kezia Dobson & Kent A. Riemondy & Samantha Pozo & Jack W. Szostak & Jay R. Hesselberth, 2025. "Nanopore sequencing of intact aminoacylated tRNAs," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    8. Liangzhen Dong & Jiayu Wang & Qing Xia, 2025. "Chemically modified tRNA enhances the translation capacity of mRNA rich in cognate codons," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    9. Vincent Gerusz & Pierre Regenass & Quentin Rousseau & Victor Moraine & Justine Dao & Xavier Lavé & Shampa Das & Josée Hue Perron & Laurence Fajas Descamps & Juan Bravo & Guennaëlle Dieppois & Nachum K, 2025. "The bactericidal FabI inhibitor Debio 1453 clears antibiotic-resistant Neisseria gonorrhoeae infection in vivo," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    10. 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.

    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:16:y:2025:i:1:d:10.1038_s41467-025-62342-4. 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.