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Modeling slow-processing of toxin messenger RNAs in type-I Toxin-Antitoxin systems: post-segregational killing and noise filtering

View ORCID ProfileYusuke Himeoka, View ORCID ProfileNamiko Mitarai
doi: https://doi.org/10.1101/407288
Yusuke Himeoka
The Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, Copenhagen, 2100-DK, Denmark
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Namiko Mitarai
The Niels Bohr Institute, University of Copenhagen, Blegdamsvej 17, Copenhagen, 2100-DK, Denmark
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Abstract

In type-I toxin-antitoxin (TA) systems, the action of growth-inhibiting toxin proteins is counteracted by the antitoxin small RNAs (sRNAs) that prevent the translation of toxin messenger RNAs (mRNAs). When a TA module is encoded on a plasmid, the short lifetime of antitoxin sRNA compared to toxin mRNAs mediates post-segregational killing (PSK) that contribute the plasmid maintenance, while some of the chromosomal encoded TA loci have been reported to contribute to persister formation in response to a specific upstream signal. Some of the well studied type-I TA systems such as hok/sok are known to have a rather complex regulatory mechanism. Transcribed full-length toxin mRNAs fold such that the ribosome binding site is not accessible and hence cannot be translated. The mRNAs are slowly processed by RNases, and the truncated mRNAs can be either translated or bound by antitoxin sRNA to be quickly degraded. We analyze the role of this extra processing by a mathematical model. We first consider the PSK scenario, and demonstrate that the extra processing compatibly ensures the high toxin expression upon complete plasmid loss, without inducing toxin expression upon acquisition of a plasmid or decrease of plasmid number to a non-zero number. We further show that the extra processing help filtering the transcription noise, avoiding random activation of toxins in transcriptionally regulated TA systems as seen in chromosomal ones. The present model highlights impacts of the slow processing reaction, offering insights on why the slow processing reactions are commonly identified in multiple type-I TA systems.

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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 04, 2018.
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Modeling slow-processing of toxin messenger RNAs in type-I Toxin-Antitoxin systems: post-segregational killing and noise filtering
Yusuke Himeoka, Namiko Mitarai
bioRxiv 407288; doi: https://doi.org/10.1101/407288
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Modeling slow-processing of toxin messenger RNAs in type-I Toxin-Antitoxin systems: post-segregational killing and noise filtering
Yusuke Himeoka, Namiko Mitarai
bioRxiv 407288; doi: https://doi.org/10.1101/407288

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