IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50627-z.html
   My bibliography  Save this article

Global regulation via modulation of ribosome pausing by the ABC-F protein EttA

Author

Listed:
  • Farès Ousalem

    (Institut de Biologie Physico-Chimique
    Université Paris Saclay, Institut de Cancérologie Gustave Roussy)

  • Saravuth Ngo

    (Institut de Biologie Physico-Chimique)

  • Thomas Oïffer

    (Institut de Biologie Physico-Chimique)

  • Amin Omairi-Nasser

    (Institut de Biologie Physico-Chimique)

  • Marion Hamon

    (FR550)

  • Laura Monlezun

    (Institut de Biologie Physico-Chimique)

  • Grégory Boël

    (Institut de Biologie Physico-Chimique)

Abstract

Having multiple rounds of translation of the same mRNA creates dynamic complexities along with opportunities for regulation related to ribosome pausing and stalling at specific sequences. Yet, mechanisms controlling these critical processes and the principles guiding their evolution remain poorly understood. Through genetic, genomic, physiological, and biochemical approaches, we demonstrate that regulating ribosome pausing at specific amino acid sequences can produce ~2-fold changes in protein expression levels which strongly influence cell growth and therefore evolutionary fitness. We demonstrate, both in vivo and in vitro, that the ABC-F protein EttA directly controls the translation of mRNAs coding for a subset of enzymes in the tricarboxylic acid (TCA) cycle and its glyoxylate shunt, which modulates growth in some chemical environments. EttA also modulates expression of specific proteins involved in metabolically related physiological and stress-response pathways. These regulatory activities are mediated by EttA rescuing ribosomes paused at specific patterns of negatively charged residues within the first 30 amino acids of nascent proteins. We thus establish a unique global regulatory paradigm based on sequence-specific modulation of translational pausing.

Suggested Citation

  • Farès Ousalem & Saravuth Ngo & Thomas Oïffer & Amin Omairi-Nasser & Marion Hamon & Laura Monlezun & Grégory Boël, 2024. "Global regulation via modulation of ribosome pausing by the ABC-F protein EttA," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50627-z
    DOI: 10.1038/s41467-024-50627-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50627-z
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-50627-z?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. Ting Su & Toshiaki Izawa & Matthias Thoms & Yui Yamashita & Jingdong Cheng & Otto Berninghausen & F. Ulrich Hartl & Toshifumi Inada & Walter Neupert & Roland Beckmann, 2019. "Structure and function of Vms1 and Arb1 in RQC and mitochondrial proteome homeostasis," Nature, Nature, vol. 570(7762), pages 538-542, June.
    2. Yosuke Ito & Yuhei Chadani & Tatsuya Niwa & Ayako Yamakawa & Kodai Machida & Hiroaki Imataka & Hideki Taguchi, 2022. "Nascent peptide-induced translation discontinuation in eukaryotes impacts biased amino acid usage in proteomes," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Mattia Zampieri & Manuel Hörl & Florian Hotz & Nicola F. Müller & Uwe Sauer, 2019. "Regulatory mechanisms underlying coordination of amino acid and glucose catabolism in Escherichia coli," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    4. 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.
    5. Zhicheng Cui & Xiaojun Li & Joonyoung Shin & Howard Gamper & Ya-Ming Hou & James C. Sacchettini & Junjie Zhang, 2022. "Interplay between an ATP-binding cassette F protein and the ribosome from Mycobacterium tuberculosis," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Corentin R. Fostier & Farès Ousalem & Elodie C. Leroy & Saravuth Ngo & Heddy Soufari & C. Axel Innis & Yaser Hashem & Grégory Boël, 2023. "Regulation of the macrolide resistance ABC-F translation factor MsrD," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    7. Bertrand Beckert & Elodie C. Leroy & Shanmugapriya Sothiselvam & Lars V. Bock & Maxim S. Svetlov & Michael Graf & Stefan Arenz & Maha Abdelshahid & Britta Seip & Helmut Grubmüller & Alexander S. Manki, 2021. "Structural and mechanistic basis for translation inhibition by macrolide and ketolide antibiotics," Nature Communications, Nature, vol. 12(1), pages 1-15, 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. Corentin R. Fostier & Farès Ousalem & Elodie C. Leroy & Saravuth Ngo & Heddy Soufari & C. Axel Innis & Yaser Hashem & Grégory Boël, 2023. "Regulation of the macrolide resistance ABC-F translation factor MsrD," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Pekka Jaako & Alexandre Faille & Shengjiang Tan & Chi C. Wong & Norberto Escudero-Urquijo & Pablo Castro-Hartmann & Penny Wright & Christine Hilcenko & David J. Adams & Alan J. Warren, 2022. "eIF6 rebinding dynamically couples ribosome maturation and translation," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    3. Chih-Wei Chen & Nadja Leimer & Egor A. Syroegin & Clémence Dunand & Zackery P. Bulman & Kim Lewis & Yury S. Polikanov & Maxim S. Svetlov, 2023. "Structural insights into the mechanism of overcoming Erm-mediated resistance by macrolides acting together with hygromycin-A," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Gaoyang Li & Li Liu & Wei Du & Huansheng Cao, 2023. "Local flux coordination and global gene expression regulation in metabolic modeling," Nature Communications, Nature, vol. 14(1), pages 1-18, 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:15:y:2024:i:1:d:10.1038_s41467-024-50627-z. 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.