A-to-I mRNA editing in bacteria can affect protein sequence, disulfide bond formation, and function

Area of Science:

• Molecular Biology
• Bacterial Genetics
• RNA Biology

Background:

• Adenosine-to-inosine (A-to-I) mRNA editing alters genetic information at the RNA level, affecting protein sequence and function in eukaryotes.
• The capacity of A-to-I mRNA editing to recode protein sequences and influence protein function in bacteria remained uncharacterized at the protein level.

Purpose of the Study:

• To demonstrate A-to-I mRNA editing's direct recoding of protein sequences in bacteria at both RNA and protein levels.
• To investigate the impact of A-to-I mRNA editing on bacterial protein function, specifically the HokB toxin.
• To explore the role of A-to-I mRNA editing in regulating disulfide bond formation in bacteria.

Main Methods:

• RNA and protein level analysis of A-to-I mRNA editing in Escherichia coli.
• Assessment of HokB toxin activity and its correlation with mRNA editing.
• Investigation of in vivo disulfide bond formation in relation to HokB function.

Main Results:

• A-to-I mRNA editing was shown to directly recode tyrosine to cysteine in the HokB toxin.
• Edited HokB exhibited increased toxicity, leading to bacterial death or premature entry into the stationary phase.
• In vivo disulfide bond formation was identified as the mechanism underlying the functional impact of A-to-I mRNA editing on HokB.

Conclusions:

• A-to-I mRNA editing directly recodes protein sequences and regulates protein function in bacteria, exemplified by HokB.
• This RNA editing mechanism provides a novel way to control disulfide bond formation in bacteria.
• The conservation of hokB mRNA editing in pathogenic bacteria suggests significant functional and potential clinical relevance.