Landscape and dynamics of TadA-dependent RNA editing in Escherichia coli reveal a role in nutrient-rich growth

Adenosine-to-inosine (A-to-I) mRNA editing alters genetic information post-transcriptionally and can impact protein sequence and function, yet its regulation in bacteria remains unclear. Here, we profiled A-to-I editing in Escherichia coli across nutrient-rich Luria-Bertani (LB) and minimal M9 media and different growth phases. Our analysis expanded the repertoire of TadA-dependent A-to-I edited mRNAs to 27, including 12 novel sites, and revealed that editing levels were dynamic and markedly increased at the stationary phase in LB but not in M9. Editing levels were independent of mRNA expression yet correlated with tRNA-Arg2 downregulation, and overexpressing tRNA-Arg2 reduced mRNA editing, demonstrating substrate competition for TadA, the sole bacterial tRNA adenosine deaminase. Mutants with TadA-deficient editing or reduced tRNA-Arg2 expression displayed similar LB-specific growth defects. Moreover, tRNA-Arg2 expression, tRNA-Arg2-dependent codon usage, and tRNA-Arg2 editing were all elevated in LB compared to M9. These findings establish regulatory principles for bacterial RNA editing, implicate tRNA editing in nutrient-responsive fitness, and provide a framework to explore the physiological roles of mRNA editing.IMPORTANCEAdenosine-to-inosine (A-to-I) mRNA editing is a recently discovered post-transcriptional mechanism in bacteria, yet its regulation and physiological roles remain poorly understood. In this study, we expand the catalog of TadA-dependent mRNA editing events in Escherichia coli and identify key regulatory factors influencing editing levels, including nutrient availability, growth phase, and tRNA-Arg2 expression. Linking altered tRNA-Arg2 levels and editing to growth defects specifically in rich medium further demonstrates that tRNA editing contributes to nutrient-responsive fitness. Together, these findings establish a framework to explore bacterial RNA editing as a regulated process with potential implications for environmental adaptation and cellular function.