Three new RelE‐homologous mRNA interferases of <i>Escherichia coli</i> differentially induced by environmental stresses

Christensen-Dalsgaard, Mikkel; Jørgensen, Mikkel Girke; Gerdes, Kenn

doi:10.1111/j.1365-2958.2009.06969.x

Cited by 207 publications

(219 citation statements)

References 66 publications

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“…The antitoxins that regulate the activities of the mRNases are Lon substrates (21,27,28). Consequently, Lon is required for activation of the mRNases.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, if an mRNase is in excess of its cognate antitoxin, the mRNase destabilizes the promoter-operator complex, and thereby induces TA operon transcription (26). The TA operons of E. coli that encode mRNases are induced by amino acid starvation via a Lon (Long Form Filament)-dependent mechanism (21,27,28). Direct evidence of Lon degradation of antitoxins has been obtained for RelB, MqsA, and YefM (27,29) (Fig.…”

mentioning

confidence: 99%

“…In all cases, ectopic production of the mRNases leads to a rapid degradation of mRNA and shut-down of translation (14,(19)(20)(21). Six of the mRNases (RelE, YoeB, HigB, YhaV, YafO, and YafQ) cleave mRNA positioned at the ribosomal A site (14,15,(21)(22)(23)(24), whereas the other 4 (MazF, ChpB, MqsR, and HicA) cleave RNA sitespecifically, independent of the ribosomes (19,20,25). The 10 mRNases and their cognate antitoxins are encoded by bicistronic operons that are autoregulated by the antitoxins, which bind to operator sequences in the TA promoter regions (10).…”

mentioning

confidence: 99%

“…The first indication that the mRNases might be involved in persistence came from the observation that their ectopic overproduction not only very efficiently inhibited translation (consistent with mRNA cleavage) but induced dormancy from which the cells could be rapidly resuscitated by the induction of cognate antitoxin genes (21,30,31). Cells overproducing TA-encoded mRNases were, similar to persister cells, tolerant to antibiotics (32)(33)(34)(35).…”

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confidence: 99%

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RETRACTED: Bacterial persistence by RNA endonucleases

Maisonneuve

Shakespeare

Jørgensen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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459

557

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Bacteria form persisters, individual cells that are highly tolerant to different types of antibiotics. Persister cells are genetically identical to nontolerant kin but have entered a dormant state in which they are recalcitrant to the killing activity of the antibiotics. The molecular mechanisms underlying bacterial persistence are unknown. Here, we show that the ubiquitous Lon (Long Form Filament) protease and mRNA endonucleases (mRNases) encoded by toxin-antitoxin (TA) loci are required for persistence in Escherichia coli . Successive deletion of the 10 mRNase-encoding TA loci of E . coli progressively reduced the level of persisters, showing that persistence is a phenotype common to TA loci. In all cases tested, the antitoxins, which control the activities of the mRNases, are Lon substrates. Consistently, cells lacking lon generated a highly reduced level of persisters. Moreover, Lon overproduction dramatically increased the levels of persisters in wild-type cells but not in cells lacking the 10 mRNases. These results support a simple model according to which mRNases encoded by TA loci are activated in a small fraction of growing cells by Lon-mediated degradation of the antitoxins. Activation of the mRNases, in turn, inhibits global cellular translation, and thereby induces dormancy and persistence. Many pathogenic bacteria known to enter dormant states have a plethora of TA genes. Therefore, in the future, the discoveries described here may lead to a mechanistic understanding of the persistence phenomenon in pathogenic bacteria.

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“…The antitoxins that regulate the activities of the mRNases are Lon substrates (21,27,28). Consequently, Lon is required for activation of the mRNases.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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RETRACTED: Bacterial persistence by RNA endonucleases

Maisonneuve

Shakespeare

Jørgensen

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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459

557

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“…Recently, we determined the crystal structures of MqsA alone and the MqsR⅐MqsA complex and showed that the mqsRA operon defines a novel family of TA systems in E. coli, in which MqsR is the toxin and MqsA is the antitoxin (19). The structure revealed that the MqsR toxin is a ribonuclease belonging to the RelE bacterial toxin family (19,34,35). MqsR is unique because it is the first toxin linked to biofilms and quorum sensing (33) and is the first toxin that, when deleted, decreases persister cell formation (31).…”

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confidence: 99%

Structure of the Escherichia coli Antitoxin MqsA (YgiT/b3021) Bound to Its Gene Promoter Reveals Extensive Domain Rearrangements and the Specificity of Transcriptional Regulation

Brown¹,

Wood

Peti³

et al. 2011

Journal of Biological Chemistry

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Bacterial cultures, especially biofilms, produce a small number of persister cells, a genetically identical subpopulation of wild type cells that are metabolically dormant, exhibit multidrug tolerance, and are highly enriched in bacterial toxins. The gene most highly up-regulated in Escherichia coli persisters is mqsR, a ribonuclease toxin that, along with mqsA, forms a novel toxin⅐antitoxin (TA) system. Like all known TA systems, both the MqsR⅐MqsA complex and MqsA alone regulate their own transcription. Despite the importance of TA systems in persistence and biofilms, very little is known about how TA modules, and antitoxins in particular, bind and recognize DNA at a molecular level. Here, we report the crystal structure of MqsA bound to a 26-bp fragment from the mqsRA promoter. We show that MqsA binds DNA predominantly via its C-terminal helix-turn-helix domain, with direct binding of recognition helix residues Asn 97 and Arg 101 to the DNA major groove. Unexpectedly, the structure also revealed that the MqsA N-terminal domain interacts with the DNA phosphate backbone. This results in a more than 105°rotation of the Nterminal domains between the free and complexed states, an unprecedented rearrangement for an antitoxin. The structure also shows that MqsA bends the DNA by more than 55°in order to achieve symmetrical binding. Finally, using a combination of biochemical and NMR studies, we show that the DNA sequence specificity of MqsA is mediated by direct readout.

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Translation‐dependent mRNA cleavage by YhaV in Escherichia coli

et al. 2017

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Many bacteria have toxin–antitoxin (TA) systems, where toxin gene expression inhibits their own cell growth. mRNA is one of the well‐known targets of the toxins in the type II toxin–antitoxin systems. Here, we examined the ribosome dependency of the endoribonuclease activity of YhaV, one of the toxins in type II TA systems, on mRNA in vitro and in vivo. A polysome profiling assay revealed that YhaV is bound to the 70S ribosomes and 50S ribosomal subunits. Moreover, we found that while YhaV cleaves ompF and lpp mRNAs in a translation‐dependent manner, they did not cleave the 5′ untranslated region in primer extension experiments. From these results, we conclude that YhaV is a ribosome‐dependent toxin that cleaves mRNA in a translation‐dependent manner.

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Three new RelE‐homologous mRNA interferases of Escherichia coli differentially induced by environmental stresses

Cited by 207 publications

References 66 publications

RETRACTED: Bacterial persistence by RNA endonucleases

RETRACTED: Bacterial persistence by RNA endonucleases

Structure of the Escherichia coli Antitoxin MqsA (YgiT/b3021) Bound to Its Gene Promoter Reveals Extensive Domain Rearrangements and the Specificity of Transcriptional Regulation

Translation‐dependent mRNA cleavage by YhaV in Escherichia coli

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