Nucleotidyltransferase toxin MenT extends aminoacyl acceptor ends of serine tRNAs to control Mycobacterium tuberculosis growth
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 tRNA<sup>Ser</sup>, to which long stretches of cytidines are added. Furthermore, transcriptomic-wide analysis of MenT3 targets in M. tuberculosis identifies tRNA<sup>Ser</sup> 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 tRNA<sup>Ser</sup> in M. tuberculosis is detected, likely reflecting the importance of MenT3 during infection.
Authors
- Xibing Xu (ORCID: https://orcid.org/0000-0002-8055-8674)
- Tom J Arrowsmith (ORCID: https://orcid.org/0009-0001-9079-9973)
- Tim R. Blower (ORCID: https://orcid.org/0000-0002-7390-6458)
- Roland Barriot (ORCID: https://orcid.org/0000-0003-0298-2696)
- Claude Gutierrez (ORCID: https://orcid.org/0000-0003-1777-0223)
- B. F. Usher (ORCID: https://orcid.org/0000-0002-2649-1210)
- Pierre Genevaux (ORCID: https://orcid.org/0000-0001-7539-3126)
- Peter Redder (ORCID: https://orcid.org/0000-0002-3619-632X)
- Olivier Neyrolles (ORCID: https://orcid.org/0000-0003-0047-5885)
- Bertille Voisin (ORCID: https://orcid.org/0009-0001-1090-1537)
- Xue Han (ORCID: https://orcid.org/0009-0009-3146-9155)
- C. Pagès
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université Toulouse III - Paul Sabatier (FR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- Durham University (GB)
- Institut de Pharmacologie et de Biologie Structurale (FR)
- Laboratoire de Microbiologie et Génétique Moléculaires (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-06
- DOI
- https://doi.org/10.1038/s41467-024-53931-w
- Citations
- 3
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.70
Funders
- Agence Nationale de la Recherche
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Fondation pour la Recherche Médicale
- Centre National de la Recherche Scientifique