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Toxin-mediated ribosome stalling reprograms the Mycobacterium tuberculosis proteome
Mycobacterium tuberculosis readily adapts to survive a wide range of assaults by modifying its physiology and establishing a latent tuberculosis (TB) infection. Here we report a sophisticated mode of regulation by a tRNA-cleaving toxin that enlists highly selective ribosome stalling to recalibrate t...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620280/ https://www.ncbi.nlm.nih.gov/pubmed/31292443 http://dx.doi.org/10.1038/s41467-019-10869-8 |
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author | Barth, Valdir C. Zeng, Ju-Mei Vvedenskaya, Irina O. Ouyang, Ming Husson, Robert N. Woychik, Nancy A. |
author_facet | Barth, Valdir C. Zeng, Ju-Mei Vvedenskaya, Irina O. Ouyang, Ming Husson, Robert N. Woychik, Nancy A. |
author_sort | Barth, Valdir C. |
collection | PubMed |
description | Mycobacterium tuberculosis readily adapts to survive a wide range of assaults by modifying its physiology and establishing a latent tuberculosis (TB) infection. Here we report a sophisticated mode of regulation by a tRNA-cleaving toxin that enlists highly selective ribosome stalling to recalibrate the transcriptome and remodel the proteome. This toxin, MazF-mt9, exclusively inactivates one isoacceptor tRNA, tRNA(Lys43-UUU), through cleavage at a single site within its anticodon (UU↓U). Because wobble rules preclude compensation for loss of tRNA(Lys43-UUU) by the second M. tuberculosis lysine tRNA, tRNA(Lys19-CUU), ribosome stalling occurs at in-frame cognate AAA Lys codons. Consequently, the transcripts harboring these stalled ribosomes are selectively cleaved by specific RNases, leading to their preferential deletion. This surgically altered transcriptome generates concomitant changes to the proteome, skewing synthesis of newly synthesized proteins away from those rich in AAA Lys codons toward those harboring few or no AAA codons. This toxin-mediated proteome reprogramming may work in tandem with other pathways to facilitate M. tuberculosis stress survival. |
format | Online Article Text |
id | pubmed-6620280 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-66202802019-07-15 Toxin-mediated ribosome stalling reprograms the Mycobacterium tuberculosis proteome Barth, Valdir C. Zeng, Ju-Mei Vvedenskaya, Irina O. Ouyang, Ming Husson, Robert N. Woychik, Nancy A. Nat Commun Article Mycobacterium tuberculosis readily adapts to survive a wide range of assaults by modifying its physiology and establishing a latent tuberculosis (TB) infection. Here we report a sophisticated mode of regulation by a tRNA-cleaving toxin that enlists highly selective ribosome stalling to recalibrate the transcriptome and remodel the proteome. This toxin, MazF-mt9, exclusively inactivates one isoacceptor tRNA, tRNA(Lys43-UUU), through cleavage at a single site within its anticodon (UU↓U). Because wobble rules preclude compensation for loss of tRNA(Lys43-UUU) by the second M. tuberculosis lysine tRNA, tRNA(Lys19-CUU), ribosome stalling occurs at in-frame cognate AAA Lys codons. Consequently, the transcripts harboring these stalled ribosomes are selectively cleaved by specific RNases, leading to their preferential deletion. This surgically altered transcriptome generates concomitant changes to the proteome, skewing synthesis of newly synthesized proteins away from those rich in AAA Lys codons toward those harboring few or no AAA codons. This toxin-mediated proteome reprogramming may work in tandem with other pathways to facilitate M. tuberculosis stress survival. Nature Publishing Group UK 2019-07-10 /pmc/articles/PMC6620280/ /pubmed/31292443 http://dx.doi.org/10.1038/s41467-019-10869-8 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Barth, Valdir C. Zeng, Ju-Mei Vvedenskaya, Irina O. Ouyang, Ming Husson, Robert N. Woychik, Nancy A. Toxin-mediated ribosome stalling reprograms the Mycobacterium tuberculosis proteome |
title | Toxin-mediated ribosome stalling reprograms the Mycobacterium tuberculosis proteome |
title_full | Toxin-mediated ribosome stalling reprograms the Mycobacterium tuberculosis proteome |
title_fullStr | Toxin-mediated ribosome stalling reprograms the Mycobacterium tuberculosis proteome |
title_full_unstemmed | Toxin-mediated ribosome stalling reprograms the Mycobacterium tuberculosis proteome |
title_short | Toxin-mediated ribosome stalling reprograms the Mycobacterium tuberculosis proteome |
title_sort | toxin-mediated ribosome stalling reprograms the mycobacterium tuberculosis proteome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620280/ https://www.ncbi.nlm.nih.gov/pubmed/31292443 http://dx.doi.org/10.1038/s41467-019-10869-8 |
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