Adenosine (A) to inosine (I) RNA editing is widespread in eukaryotes. In prokaryotes, however, A-to-I RNA editing was only reported to occur in tRNAs but not in protein-coding genes. By comparing DNA and RNA sequences of Escherichia coli, we show for the first time that A-to-I editing occurs also in prokaryotic mRNAs and has the potential to affect the translated proteins and cell physiology. We found 15 novel A-to-I editing events, of which 12 occurred within known protein-coding genes where they always recode a tyrosine (TAC) into a cysteine (TGC) codon. Furthermore, we identified the tRNA-specific adenosine deaminase (tadA) as the editing enzyme of all these editing sites, thus making it the first identified RNA editing enzyme that modifies both tRNAs and mRNAs. Interestingly, several of the editing targets are self-killing toxins that belong to evolutionarily conserved toxin-antitoxin pairs. We focused on hokB, a toxin that confers antibiotic tolerance by growth inhibition, as it demonstrated the highest level of such mRNA editing. We identified a correlated mutation pattern between the edited and a DNA hard-coded Cys residue positions in the toxin and demonstrated that RNA editing occurs in hokB in two additional bacterial species. Thus, not only the toxin is evolutionarily conserved but also the editing itself within the toxin is. Finally, we found that RNA editing in hokB increases as a function of cell density and enhances its toxicity. Our work thus demonstrates the occurrence, regulation, and functional consequences of RNA editing in bacteria.

腺苷（A）到肌苷（I）RNA编辑在真核生物中很普遍。然而，在原核生物中，据报道A-to-I RNA编辑仅在tRNA中发生，而在蛋白质编码基因中不发生。通过比较大肠杆菌的DNA和RNA序列，我们首次证明A-to-I编辑也发生在原核mRNA中，并且有可能影响翻译的蛋白质和细胞生理。我们发现了15种新颖的A对I编辑事件，其中12种发生在已知的蛋白质编码基因中，它们总是将酪氨酸（TAC）重新编码为半胱氨酸（TGC）密码子。此外，我们确定了tRNA特异性腺苷脱氨酶（tadA）作为所有这些编辑位点的编辑酶，因此使其成为第一个识别出同时修饰tRNA和mRNA的RNA编辑酶。有趣的是，一些编辑目标是自杀毒素，属于进化上保守的毒素-抗毒素对。我们专注于hokB，它是一种通过生长抑制赋予抗生素耐受性的毒素，因为它证明了此类mRNA编辑的最高水平。hokB在另外两个细菌种类中。因此，不仅毒素在进化上是保守的，而且毒素内的编辑本身也是这样。最后，我们发现hokB中的RNA编辑随细胞密度的增加而增加，并增强其毒性。因此，我们的工作证明了细菌中RNA编辑的发生，调控和功能后果。