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Dynamics of diversified A-to-I editing in Streptococcus pyogenes is governed by changes in mRNA stability

View ORCID ProfileThomas F. Wulff, Karin Hahnke, View ORCID ProfileAnne-Laure Lécrivain, Katja Schmidt, View ORCID ProfileRina Ahmed-Begrich, View ORCID ProfileKnut Finstermeier, View ORCID ProfileEmmanuelle Charpentier
doi: https://doi.org/10.1101/2023.09.19.555891
Thomas F. Wulff
1Max Planck Unit for the Science of Pathogens, 10117 Berlin, Germany
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Karin Hahnke
1Max Planck Unit for the Science of Pathogens, 10117 Berlin, Germany
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Anne-Laure Lécrivain
1Max Planck Unit for the Science of Pathogens, 10117 Berlin, Germany
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Katja Schmidt
1Max Planck Unit for the Science of Pathogens, 10117 Berlin, Germany
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Rina Ahmed-Begrich
1Max Planck Unit for the Science of Pathogens, 10117 Berlin, Germany
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Knut Finstermeier
1Max Planck Unit for the Science of Pathogens, 10117 Berlin, Germany
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Emmanuelle Charpentier
1Max Planck Unit for the Science of Pathogens, 10117 Berlin, Germany
2Institute for Biology, Humboldt University Berlin, 10115 Berlin, Germany
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  • For correspondence: research@emmanuelle-charpentier.org
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ABSTRACT

Adenosine-to-inosine (A-to-I) RNA editing plays an important role in the post-transcriptional regulation of eukaryotic cell physiology. However, our understanding of the occurrence, function and regulation of A-to-I editing in bacteria remains limited. Bacterial mRNA editing is catalysed by the deaminase TadA, which was originally described to modify a single tRNA in E. coli. Intriguingly, several bacterial species appear to perform A-to-I editing on more than one tRNA. Here, we provide evidence that in the human pathogen Streptococcus pyogenes, tRNA editing has expanded to an additional tRNA substrate. Using RNA sequencing, we identified more than 27 editing sites in the transcriptome of S. pyogenes SF370 and demonstrate that the adaptation of S. pyogenes TadA to a second tRNA substrate has also diversified the sequence context and recoding scope of mRNA editing. Based on the observation that editing is dynamically regulated in response to several infection-relevant stimuli, such as oxidative stress, we further investigated the underlying determinants of editing dynamics and identified mRNA stability as a key modulator of A-to-I editing. Overall, our findings reveal the presence and diversification of A-to-I editing in S. pyogenes and provide novel insights into the plasticity of the editome and its regulation in bacteria.

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Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted September 19, 2023.
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Dynamics of diversified A-to-I editing in Streptococcus pyogenes is governed by changes in mRNA stability
Thomas F. Wulff, Karin Hahnke, Anne-Laure Lécrivain, Katja Schmidt, Rina Ahmed-Begrich, Knut Finstermeier, Emmanuelle Charpentier
bioRxiv 2023.09.19.555891; doi: https://doi.org/10.1101/2023.09.19.555891
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Dynamics of diversified A-to-I editing in Streptococcus pyogenes is governed by changes in mRNA stability
Thomas F. Wulff, Karin Hahnke, Anne-Laure Lécrivain, Katja Schmidt, Rina Ahmed-Begrich, Knut Finstermeier, Emmanuelle Charpentier
bioRxiv 2023.09.19.555891; doi: https://doi.org/10.1101/2023.09.19.555891

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