RT Journal
A1 Bar-Yaacov, Dan
A1 Mordret, Ernest
A1 Towers, Ruth
A1 Biniashvili, Tammy
A1 Soyris, Clara
A1 Schwartz, Schraga
A1 Dahan, Orna
A1 Pilpel, Yitzhak
T1 RNA editing in bacteria recodes multiple proteins and regulates an evolutionarily conserved toxin-antitoxin system
JF Genome Research 
JO Genome Research 
YR 2017 
FD October 01 
VO 27 
IS 10 
SP 1696 
OP 1703 
DO 10.1101/gr.222760.117 
UL http://genome.cshlp.org/content/27/10/1696.abstract 
AB 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.