Work

A type VI secretion ADP-ribosyltransferase Rhs toxin selectively modifies charged tRNAThr(GGU) anticodon loops to block ACC codon decoding

Year: 2026

Type: article

Abstract: The type VI secretion system (T6SS) is a sophisticated machine that uses a contractile mechanism to deliver antibacterial toxins into neighboring cells, hence participating to interbacterial competition and pathogenesis. Here, we characterize the T6SS-associated rearrangement hotspot RhsF polymorphic toxin from Chromobacterium violaceum. Toxicity assays showed that the RhsF C-terminal extension, TreThr, is a cytoplasmic-acting antibacterial toxin, which is neutralized by the downstream immunity protein. Structural modeling and mutagenesis demonstrated that TreThr belongs to the ADP-ribosyltransferase (ART) family, adopting a canonical ART fold. Using coupled in vitro transcription-translation assays, we found that TreThr inhibits protein synthesis in a Nicotinamide Adenine Dinucleotide (NAD)-dependent manner, through isoacceptor-specific ADP-ribosylation of transfer RNAs (tRNAs). Biotin-NAD labeling experiments and mapping further revealed that TreThr modifies the GGU anticodon of charged thrT and thrV tRNA isoacceptors and prevents decoding of threonine ACC codons.

Source: Nucleic Acids Research

DOI: 10.1093/nar/gkag922

Authors: Maïalène Chabalier, Jonas B Desjardins, Julius Martinkus, Eric Cascales

Institutions: Centre National de la Recherche Scientifique, Aix-Marseille Université, Laboratoire d'Ingénierie des Systèmes Macromoléculaires

Language: English

Topic: RNA and protein synthesis mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,992

Funders: Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Centre National de la Recherche Scientifique, Fondation Bettencourt Schueller