A-to-I mRNA editing recodes CqsA and affects T6SS-mediated killing in Vibrio

Abstract

Adenosine-to-inosine (A-to-I) RNA editing alters genetic information post-transcriptionally, yet its ecological and evolutionary significance in bacteria remains largely unexplored. Here, we show that endogenous RNA editing has functional consequences in bacteria. Using Vibrio alginolyticus as a model, we identified 38 editing events--the highest number reported for any bacterium to date. Editing frequencies varied across growth phases and occurred within a shorter conserved sequence motif than observed in other bacteria, suggesting species-specific determinants. The mRNA of the quorum-sensing (QS) autoinducer synthase cqsA was the most extensively edited, with 70-90% of transcripts modified. Phylogenetic and experimental analyses revealed that cqsA editing is evolutionarily conserved across diverse Vibrio species, including human pathogens. Protein mass spectrometry showed that editing replaces a tyrosine with a cysteine residue at position 193 of endogenously expressed CqsA without altering its expression or the canonical downstream QS signaling pathway. However, we found that endogenous editing of cqsA alters the expression of a subset of genes and is required for efficient type VI secretion system (T6SS)-mediated interbacterial killing. Together, these findings suggest that CqsA has additional roles beyond its canonical QS function and that RNA editing can modulate bacterial physiology. SignificanceBacteria are haploid organisms having a single copy of each gene. A-to-I RNA editing can change genetic information at the RNA level, creating protein isoforms in bacteria, but its functional impact remains unclear. Here we show that a marine Vibrio species has at least 38 edited RNAs--the highest number reported in any bacterium. We further show that editing of the quorum-sensing synthase cqsA is widespread across Vibrio species and recodes CqsA protein sequence without affecting canonical quorum sensing. Instead, editing alters expression of a focused gene set, including the type VI secretion system component hcp1, and is required for efficient T6SS-mediated interbacterial killing. Our findings uncover a conserved, quorum-sensing-independent role for CqsA in bacterial competition.