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Global Analysis of the Specificities and Targets of Endoribonucleases from Escherichia coli Toxin-Antitoxin Systems

Toxin-antitoxin systems are widely distributed genetic modules typically featuring toxins that can inhibit bacterial growth and antitoxins that can reverse inhibition. Although Escherichia coli encodes 11 toxins with known or putative endoribonuclease activity, the targets of most of these toxins re...

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Autores principales: Culviner, Peter H., Nocedal, Isabel, Fortune, Sarah M., Laub, Michael T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546651/
https://www.ncbi.nlm.nih.gov/pubmed/34544284
http://dx.doi.org/10.1128/mBio.02012-21
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author Culviner, Peter H.
Nocedal, Isabel
Fortune, Sarah M.
Laub, Michael T.
author_facet Culviner, Peter H.
Nocedal, Isabel
Fortune, Sarah M.
Laub, Michael T.
author_sort Culviner, Peter H.
collection PubMed
description Toxin-antitoxin systems are widely distributed genetic modules typically featuring toxins that can inhibit bacterial growth and antitoxins that can reverse inhibition. Although Escherichia coli encodes 11 toxins with known or putative endoribonuclease activity, the targets of most of these toxins remain poorly characterized. Using a new RNA sequencing (RNA-seq) pipeline that enables the mapping and quantification of RNA cleavage with single-nucleotide resolution, we characterized the targets and specificities of 9 endoribonuclease toxins from E. coli. We found that these toxins use low-information cleavage motifs to cut a significant proportion of mRNAs in E. coli, but not tRNAs or the rRNAs from mature ribosomes. However, all the toxins, including those that are ribosome dependent and cleave only translated RNA, inhibit ribosome biogenesis. This inhibition likely results from the cleavage of ribosomal protein transcripts, which disrupts the stoichiometry and biogenesis of new ribosomes and causes the accumulation of aberrant ribosome precursors. Collectively, our results provide a comprehensive, global analysis of endoribonuclease-based toxin-antitoxin systems in E. coli and support the conclusion that, despite their diversity, each disrupts translation and ribosome biogenesis.
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spelling pubmed-85466512021-11-04 Global Analysis of the Specificities and Targets of Endoribonucleases from Escherichia coli Toxin-Antitoxin Systems Culviner, Peter H. Nocedal, Isabel Fortune, Sarah M. Laub, Michael T. mBio Research Article Toxin-antitoxin systems are widely distributed genetic modules typically featuring toxins that can inhibit bacterial growth and antitoxins that can reverse inhibition. Although Escherichia coli encodes 11 toxins with known or putative endoribonuclease activity, the targets of most of these toxins remain poorly characterized. Using a new RNA sequencing (RNA-seq) pipeline that enables the mapping and quantification of RNA cleavage with single-nucleotide resolution, we characterized the targets and specificities of 9 endoribonuclease toxins from E. coli. We found that these toxins use low-information cleavage motifs to cut a significant proportion of mRNAs in E. coli, but not tRNAs or the rRNAs from mature ribosomes. However, all the toxins, including those that are ribosome dependent and cleave only translated RNA, inhibit ribosome biogenesis. This inhibition likely results from the cleavage of ribosomal protein transcripts, which disrupts the stoichiometry and biogenesis of new ribosomes and causes the accumulation of aberrant ribosome precursors. Collectively, our results provide a comprehensive, global analysis of endoribonuclease-based toxin-antitoxin systems in E. coli and support the conclusion that, despite their diversity, each disrupts translation and ribosome biogenesis. American Society for Microbiology 2021-09-21 /pmc/articles/PMC8546651/ /pubmed/34544284 http://dx.doi.org/10.1128/mBio.02012-21 Text en Copyright © 2021 Culviner et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Culviner, Peter H.
Nocedal, Isabel
Fortune, Sarah M.
Laub, Michael T.
Global Analysis of the Specificities and Targets of Endoribonucleases from Escherichia coli Toxin-Antitoxin Systems
title Global Analysis of the Specificities and Targets of Endoribonucleases from Escherichia coli Toxin-Antitoxin Systems
title_full Global Analysis of the Specificities and Targets of Endoribonucleases from Escherichia coli Toxin-Antitoxin Systems
title_fullStr Global Analysis of the Specificities and Targets of Endoribonucleases from Escherichia coli Toxin-Antitoxin Systems
title_full_unstemmed Global Analysis of the Specificities and Targets of Endoribonucleases from Escherichia coli Toxin-Antitoxin Systems
title_short Global Analysis of the Specificities and Targets of Endoribonucleases from Escherichia coli Toxin-Antitoxin Systems
title_sort global analysis of the specificities and targets of endoribonucleases from escherichia coli toxin-antitoxin systems
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546651/
https://www.ncbi.nlm.nih.gov/pubmed/34544284
http://dx.doi.org/10.1128/mBio.02012-21
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