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Nucleotidyltransferase toxin MenT extends aminoacyl acceptor ends of serine tRNAs to control Mycobacterium tuberculosis growth

Author

Listed:
  • Xibing Xu

    (UPS)

  • Roland Barriot

    (UPS)

  • Bertille Voisin

    (UPS)

  • Tom J. Arrowsmith

    (Durham University)

  • Ben Usher

    (Durham University)

  • Claude Gutierrez

    (UPS)

  • Xue Han

    (UPS)

  • Carine Pagès

    (UPS)

  • Peter Redder

    (UPS)

  • Tim R. Blower

    (Durham University)

  • Olivier Neyrolles

    (UPS)

  • Pierre Genevaux

    (UPS)

Abstract

Toxins of toxin-antitoxin systems use diverse mechanisms to inhibit bacterial growth. In this study, we characterize the translation inhibitor toxin MenT3 of Mycobacterium tuberculosis, the bacterium responsible for tuberculosis in humans. We show that MenT3 is a robust cytidine specific tRNA nucleotidyltransferase in vitro, capable of modifying the aminoacyl acceptor ends of most tRNA but with a marked preference for tRNASer, to which long stretches of cytidines are added. Furthermore, transcriptomic-wide analysis of MenT3 targets in M. tuberculosis identifies tRNASer as the sole target of MenT3 and reveals significant detoxification attempts by the essential CCA-adding enzyme PcnA in response to MenT3. Finally, under physiological conditions, only in the presence the native menAT3 operon, an active pool of endogenous MenT3 targeting tRNASer in M. tuberculosis is detected, likely reflecting the importance of MenT3 during infection.

Suggested Citation

  • Xibing Xu & Roland Barriot & Bertille Voisin & Tom J. Arrowsmith & Ben Usher & Claude Gutierrez & Xue Han & Carine Pagès & Peter Redder & Tim R. Blower & Olivier Neyrolles & Pierre Genevaux, 2024. "Nucleotidyltransferase toxin MenT extends aminoacyl acceptor ends of serine tRNAs to control Mycobacterium tuberculosis growth," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53931-w
    DOI: 10.1038/s41467-024-53931-w
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    References listed on IDEAS

    as
    1. Tom J. Arrowsmith & Xibing Xu & Shangze Xu & Ben Usher & Peter Stokes & Megan Guest & Agnieszka K. Bronowska & Pierre Genevaux & Tim R. Blower, 2024. "Inducible auto-phosphorylation regulates a widespread family of nucleotidyltransferase toxins," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Hatice Akarsu & Patricia Bordes & Moise Mansour & Donna-Joe Bigot & Pierre Genevaux & Laurent Falquet, 2019. "TASmania: A bacterial Toxin-Antitoxin Systems database," PLOS Computational Biology, Public Library of Science, vol. 15(4), pages 1-28, April.
    3. Xibing Xu & Ben Usher & Claude Gutierrez & Roland Barriot & Tom J. Arrowsmith & Xue Han & Peter Redder & Olivier Neyrolles & Tim R. Blower & Pierre Genevaux, 2023. "MenT nucleotidyltransferase toxins extend tRNA acceptor stems and can be inhibited by asymmetrical antitoxin binding," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Roger Fricker & Rebecca Brogli & Hannes Luidalepp & Leander Wyss & Michel Fasnacht & Oliver Joss & Marek Zywicki & Mark Helm & André Schneider & Marina Cristodero & Norbert Polacek, 2019. "A tRNA half modulates translation as stress response in Trypanosoma brucei," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    5. Josh Abramson & Jonas Adler & Jack Dunger & Richard Evans & Tim Green & Alexander Pritzel & Olaf Ronneberger & Lindsay Willmore & Andrew J. Ballard & Joshua Bambrick & Sebastian W. Bodenstein & David , 2024. "Accurate structure prediction of biomolecular interactions with AlphaFold 3," Nature, Nature, vol. 630(8016), pages 493-500, June.
    6. Tannu Priya Gosain & Saurabh Chugh & Zaigham Abbas Rizvi & Neeraj Kumar Chauhan & Saqib Kidwai & Krishan Gopal Thakur & Amit Awasthi & Ramandeep Singh, 2024. "Mycobacterium tuberculosis strain with deletions in menT3 and menT4 is attenuated and confers protection in mice and guinea pigs," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. Moise Mansour & Emmanuel Giudice & Xibing Xu & Hatice Akarsu & Patricia Bordes & Valérie Guillet & Donna-Joe Bigot & Nawel Slama & Gaetano D’urso & Sophie Chat & Peter Redder & Laurent Falquet & Lione, 2022. "Substrate recognition and cryo-EM structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
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