Two microbiome metabolites compete for tRNA modification to impact mammalian cell proliferation and translation quality control

Wen Zhang; Kuldeep Lahry; Denis Cipurko; Sihao Huang; Olivia Zbihley; Amanda M Sevilleja; Dominika Rudzka; Luke R Frietze; Mahdi Assari; Christopher D Katanski; Marisha Singh; Aurore Attina; Hélène Guillorit; Christopher P Watkins; Delphine Gourlain; Didier Varlet; Jennifer Falconi; Alexandre Djiane; Christophe Hirtz; Hankui Chen; Françoise Macari; Katherine Johnson; Nicolas Chevrier; Alexandre David; Tao Pan

doi:10.1038/s41556-025-01750-6

Retour

Two microbiome metabolites compete for tRNA modification to impact mammalian cell proliferation and translation quality control

Article de revue

Avec comité de lecture

Two microbiome metabolites compete for tRNA modification to impact mammalian cell proliferation and translation quality control

Wen Zhang, Kuldeep Lahry, Denis Cipurko, Sihao Huang, Olivia Zbihley, Amanda M Sevilleja, Dominika Rudzka, Luke R Frietze, Mahdi Assari, Christopher D Katanski, …

Nature cell biology, Vol.27(10), pp.1812-1826

01/10/2025

DOI: https://doi.org/10.1038/s41556-025-01750-6

PMID: 40957911

Résumé

Animals

Cell Proliferation - drug effects

Humans

Mice

Microbiota

Nucleoside Q - analogs & derivatives

Nucleoside Q - metabolism

Nucleoside Q - pharmacology

Protein Biosynthesis - drug effects

Ribosomes - metabolism

RNA, Transfer - genetics

RNA, Transfer - metabolism

The microbiome affects eukaryotic host cells via many metabolites, including the well-studied queuine as substrate for host tRNA queuosine modification. The microbial metabolite pre-queuosine 1 (preQ ) is produced in the bacterial tRNA queuosine biosynthesis pathway, with unknown effects on host cell biology. Here we show that preQ strongly represses cell proliferation in both human and mouse cells. Queuine reverses this effect by competing with preQ to modify the same tRNA. PreQ is detectable in the plasma and tissues of mice, and its injection suppresses tumour growth in a mouse cancer model. Mechanistically, preQ reduces cognate tRNA levels specifically, as well as codon-dependent translation of housekeeping genes. We identify the endoplasmic reticulum-localized inositol-requiring enzyme 1 (IRE1) ribonuclease as the enzyme responsible for the selective degradation of preQ -modified tRNAs on translating ribosomes. Our results identify two microbial metabolites competing for host tRNA modification, which elicits translation quality control and impacts cell proliferation.

Indicateurs

1 Consultations de la notice

See more details

Détails

Titre: Two microbiome metabolites compete for tRNA modification to impact mammalian cell proliferation and translation quality control
Créateurs - sans rôle: Wen Zhang - Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA
Kuldeep Lahry - IRCM, University of Montpellier, Montpellier, France
Denis Cipurko - Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA
Sihao Huang - Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA
Olivia Zbihley - Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA
Amanda M Sevilleja - Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA
Dominika Rudzka - Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA
Luke R Frietze - Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA
Mahdi Assari - Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA
Christopher D Katanski - Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA
Marisha Singh - Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA
Aurore Attina - IRMB-PPC, INM, CHU Montpellier, University of Montpellier, Montpellier, France
Hélène Guillorit - IRCM, University of Montpellier, Montpellier, France
Christopher P Watkins - Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA
Delphine Gourlain - Synthenova, Hérouville Saint Clair, France
Didier Varlet - Synthenova, Hérouville Saint Clair, France
Jennifer Falconi - IRCM, University of Montpellier, Montpellier, France
Alexandre Djiane - IRCM, University of Montpellier, Montpellier, France
Christophe Hirtz - IRMB-PPC, INM, CHU Montpellier, University of Montpellier, Montpellier, France
Hankui Chen - Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA
Françoise Macari - IRCM, University of Montpellier, Montpellier, France
Katherine Johnson - Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA
Nicolas Chevrier - Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, USA. nchevrier@uchicago.edu
Alexandre David - IRMB-PPC, INM, CHU Montpellier, University of Montpellier, Montpellier, France. alexandre.david@inserm.fr
Tao Pan - Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA. taopan@uchicago.edu
Détails de publication: Nature cell biology, Vol.27(10), pp.1812-1826
Note de subvention: RM1HG008935 / U.S. Department of Health & Human Services | National Institutes of Health (NIH) P30 DK42086 / University of Chicago (UChicago) R33CA272357 / U.S. Department of Health & Human Services | National Institutes of Health (NIH)
Identifiants: 99140117709311
Unité académique: Institut de Recherche en Cancérologie de Montpellier - IRCM; Institut des Neurosciences de Montpellier - INM
Langue: English
Type de ressource: Journal article