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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2021
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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. |
format | Online Article Text |
id | pubmed-8546651 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
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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