Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA

SK Christensen; K Pedersen; FG Hansen; K Gerdes

doi:10.1016/S0022-2836(03)00922-7

Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA

SK Christensen, K Pedersen, FG Hansen, K Gerdes

301 Citationer (Scopus)

Abstract

Prokaryotic chromosomes encode toxin-antitoxin loci, often in multiple copies. In most cases, the function of these genes is not known. The chpA (mazEF) locus of Escherichia coli has been described as a cell killing module that induces bacterial apoptosis during nutritional stress. However, we found recently that ChpAK (MazF) does not confer cell killing but rather, induces a bacteriostatic condition from which the cells could be resuscitated. Results presented here yield a mechanistic explanation for the detrimental effect on cell growth exerted by ChpAK and the homologous ChpBK protein of E. coli. We show that both proteins inhibit translation by inducing cleavage of translated mRNAs. Consistently, the inhibitory effect of the proteins was counteracted by tmRNA. Amino acid starvation induced strong transcription of chpA that depended on Lon protease but not on ppGpp. Simultaneously, ChpAK cleaved tmRNA in its coding region. Thus, ChpAK and ChpBK inhibit translation by a mechanism very similar to that of E. coli RelE. On the basis of these results, we propose a model that integrates TA loci into general prokaryotic stress physiology. (C) 2003 Elsevier Ltd. All rights reserved.

Originalsprog	Engelsk
Tidsskrift	Journal of Molecular Biology
Vol/bind	332
Udgave nummer	4
Sider (fra-til)	809-819
Antal sider	11
ISSN	0022-2836
DOI	https://doi.org/10.1016/S0022-2836(03)00922-7
Status	Udgivet - 2003
Udgivet eksternt	Ja

Adgang til dokumentet

10.1016/S0022-2836(03)00922-7

Citationsformater

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title = "Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA",

abstract = "Prokaryotic chromosomes encode toxin-antitoxin loci, often in multiple copies. In most cases, the function of these genes is not known. The chpA (mazEF) locus of Escherichia coli has been described as a cell killing module that induces bacterial apoptosis during nutritional stress. However, we found recently that ChpAK (MazF) does not confer cell killing but rather, induces a bacteriostatic condition from which the cells could be resuscitated. Results presented here yield a mechanistic explanation for the detrimental effect on cell growth exerted by ChpAK and the homologous ChpBK protein of E. coli. We show that both proteins inhibit translation by inducing cleavage of translated mRNAs. Consistently, the inhibitory effect of the proteins was counteracted by tmRNA. Amino acid starvation induced strong transcription of chpA that depended on Lon protease but not on ppGpp. Simultaneously, ChpAK cleaved tmRNA in its coding region. Thus, ChpAK and ChpBK inhibit translation by a mechanism very similar to that of E. coli RelE. On the basis of these results, we propose a model that integrates TA loci into general prokaryotic stress physiology. (C) 2003 Elsevier Ltd. All rights reserved.",

author = "SK Christensen and K Pedersen and FG Hansen and K Gerdes",

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TY - JOUR

T1 - Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA

AU - Christensen, SK

AU - Pedersen, K

AU - Hansen, FG

AU - Gerdes, K

PY - 2003

Y1 - 2003

N2 - Prokaryotic chromosomes encode toxin-antitoxin loci, often in multiple copies. In most cases, the function of these genes is not known. The chpA (mazEF) locus of Escherichia coli has been described as a cell killing module that induces bacterial apoptosis during nutritional stress. However, we found recently that ChpAK (MazF) does not confer cell killing but rather, induces a bacteriostatic condition from which the cells could be resuscitated. Results presented here yield a mechanistic explanation for the detrimental effect on cell growth exerted by ChpAK and the homologous ChpBK protein of E. coli. We show that both proteins inhibit translation by inducing cleavage of translated mRNAs. Consistently, the inhibitory effect of the proteins was counteracted by tmRNA. Amino acid starvation induced strong transcription of chpA that depended on Lon protease but not on ppGpp. Simultaneously, ChpAK cleaved tmRNA in its coding region. Thus, ChpAK and ChpBK inhibit translation by a mechanism very similar to that of E. coli RelE. On the basis of these results, we propose a model that integrates TA loci into general prokaryotic stress physiology. (C) 2003 Elsevier Ltd. All rights reserved.

AB - Prokaryotic chromosomes encode toxin-antitoxin loci, often in multiple copies. In most cases, the function of these genes is not known. The chpA (mazEF) locus of Escherichia coli has been described as a cell killing module that induces bacterial apoptosis during nutritional stress. However, we found recently that ChpAK (MazF) does not confer cell killing but rather, induces a bacteriostatic condition from which the cells could be resuscitated. Results presented here yield a mechanistic explanation for the detrimental effect on cell growth exerted by ChpAK and the homologous ChpBK protein of E. coli. We show that both proteins inhibit translation by inducing cleavage of translated mRNAs. Consistently, the inhibitory effect of the proteins was counteracted by tmRNA. Amino acid starvation induced strong transcription of chpA that depended on Lon protease but not on ppGpp. Simultaneously, ChpAK cleaved tmRNA in its coding region. Thus, ChpAK and ChpBK inhibit translation by a mechanism very similar to that of E. coli RelE. On the basis of these results, we propose a model that integrates TA loci into general prokaryotic stress physiology. (C) 2003 Elsevier Ltd. All rights reserved.

U2 - 10.1016/S0022-2836(03)00922-7

DO - 10.1016/S0022-2836(03)00922-7

M3 - Journal article

SN - 0022-2836

VL - 332

SP - 809

EP - 819

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

IS - 4

ER -