RNA editing in bacteria recodes multiple proteins and regulates an evolutionarily conserved toxin-antitoxin system

Area of Science:

• Molecular Biology
• Genetics
• Microbiology

Background:

• Adenosine (A) to inosine (I) RNA editing is a common post-transcriptional modification in eukaryotes.
• In prokaryotes, A-to-I RNA editing was previously documented exclusively in transfer RNAs (tRNAs).

Purpose of the Study:

• To investigate the occurrence and implications of A-to-I RNA editing in prokaryotic messenger RNAs (mRNAs).
• To identify the enzyme responsible for prokaryotic mRNA editing and explore its functional consequences.

Main Methods:

• Comparative analysis of DNA and RNA sequences in *Escherichia coli*.
• Identification of novel A-to-I editing sites within protein-coding genes.
• Characterization of the editing enzyme using biochemical and genetic approaches.

Main Results:

• Discovery of 15 novel A-to-I RNA editing events in *E. coli*, with 12 occurring in protein-coding genes, consistently recoding tyrosine to cysteine.
• Identification of tRNA-specific adenosine deaminase (tadA) as the enzyme responsible for both tRNA and mRNA editing.
• Demonstration that editing in the *hokB* toxin gene increases with cell density, enhancing toxicity and conserved across bacterial species.

Conclusions:

• A-to-I RNA editing occurs in prokaryotic mRNAs, impacting protein function and cell physiology.
• The tadA enzyme is the first identified RNA editor acting on both tRNA and mRNA in prokaryotes.
• RNA editing in bacterial toxin genes is regulated and evolutionarily conserved, influencing bacterial survival and inter-bacterial interactions.