An RNA-targeting ADP-ribosyltransferase toxin uncouples mRNA stability from productive translation

ABSTRACT: mRNA modifications regulate transcript stability and translation efficiency across diverse biological systems, but the consequences of toxin-mediated mRNA modification in bacteria remain poorly understood. RhsP2 was recently identified as an RNA-targeting interbacterial ADP-ribosyltransferase toxin, but whether mRNAs are physiological substrates remained unknown. Here, we show that RhsP2 targets mRNA coding sequences and in doing so prevents their efficient translation. eCLIP-seq reveals preferential association of RhsP2 with UAA-enriched motifs and biochemical analyses showed that these sequences are preferred substrates for ribose 2′-OH ADP-ribosylation. Unexpectedly, modified mRNAs were broadly stabilized despite impaired protein synthesis, demonstrating that RhsP2 uncouples transcript stability from productive translation. Monosome- and disome-seq analyses show that RhsP2-modified mRNAs induce ribosome stalling and collision, and in vitro translation reactions demonstrate that ADP-ribosylation of mRNAs is sufficient to block translation elongation. Together, these findings establish mRNA ADP-ribosylation as a mechanism of toxin-mediated translational sabotage in which chemically modified transcripts accumulate while disrupting protein synthesis.

ORGANISM(S): Escherichia coli

PROVIDER: GSE346425 | GEO | 2026/10/08

REPOSITORIES: GEO