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PMID:15009896

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Citation

Christensen, SK, Maenhaut-Michel, G, Mine, N, Gottesman, S, Gerdes, K and Van Melderen, L (2004) Overproduction of the Lon protease triggers inhibition of translation in Escherichia coli: involvement of the yefM-yoeB toxin-antitoxin system. Mol. Microbiol. 51:1705-17

Abstract

In Escherichia coli, the Lon ATP-dependent protease is responsible for degradation of several regulatory proteins and for the elimination of abnormal proteins. Previous studies have shown that the overproduction of Lon is lethal. Here, we showed that Lon overproduction specifically inhibits translation through at least two different pathways. We have identified one of the pathways as being the chromosomal yefM-yoeB toxin-antitoxin system. The existence of a second pathway is demonstrated by the observation that the deletion of the yefM-yoeB system did not completely suppress lethality and translation inhibition. We also showed that the YoeB toxin induces cleavage of translated mRNAs and that Lon overproduction specifically activates YoeB-dependent mRNAs cleavage. Indeed, none of the other identified chromosomal toxin-antitoxin systems (relBE, mazEF, chpB and dinJ-yafQ) was involved in Lon-dependent lethality, translation inhibition and mRNA cleavage even though the RelB and MazE antitoxins are known to be Lon substrates. Based on our results and other studies, translation inhibition appears to be the key element that triggers chromosomal toxin-antitoxin systems. We propose that under Lon overproduction conditions, translation inhibition is mediated by Lon degradation of a component of the YoeB-independent pathway, in turn activating the YoeB toxin by preventing synthesis of its unstable YefM antidote.

Links

PubMed

Keywords

ATP-Dependent Proteases; Adenosine Triphosphatases/metabolism; Bacterial Toxins/metabolism; Base Sequence; Chromosomes, Bacterial; DNA Primers; Escherichia coli/enzymology; Escherichia coli/genetics; Escherichia coli Proteins/physiology; Genes, Bacterial; Genes, Lethal; Heat-Shock Proteins/biosynthesis; Heat-Shock Proteins/metabolism; Hydrolysis; Methionine/metabolism; Protease La; Protein Biosynthesis; RNA, Bacterial/genetics; RNA, Bacterial/metabolism; RNA, Messenger/genetics; RNA, Messenger/metabolism; Serine Endopeptidases/biosynthesis; Serine Endopeptidases/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

ECOLI:YOEB

involved_in

GO:0098795: mRNA destabilization-mediated gene silencing

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

ECOLI:YOEB

involved_in

GO:0098795: mRNA cleavage involved in gene silencing

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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