HicA of
            <i>Escherichia coli</i>
            Defines a Novel Family of Translation-Independent mRNA Interferases in Bacteria and Archaea

Jørgensen, Mikkel Girke; Pandey, Deo Prakash; Jaskólska, Milena; Gerdes, Kenn

doi:10.1128/jb.01013-08

Cited by 219 publications

(270 citation statements)

References 45 publications

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“…Direct evidence of Lon degradation of antitoxins has been obtained for RelB, MqsA, and YefM (27,29) (Fig. S2), whereas indirect evidence has been obtained in the cases of MazE, MazE-2 (ChpBI), HicB, YafN, and YgjM (HigA) (19,28). Hence, Lon controls the activities of the mRNases by controlling the levels of the antitoxins.…”

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confidence: 97%

“…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).…”

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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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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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confidence: 97%

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confidence: 99%

RETRACTED: Bacterial persistence by RNA endonucleases

Maisonneuve

Shakespeare

Jørgensen

et al. 2011

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

Self Cite

459

557

View full text Add to dashboard Cite

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“…On the basis of their mechanism of action, the mRNA interferases can be divided into two groups: RelE, YafQ, and YoeB are associated with the ribosome and cleave mRNA at the ribosomal A site, while MazF, ChpB, HicA, YhaV, and MqsR cleave mRNA independently of the ribosome (Pedersen et al 2003;Zhang et al 2003bZhang et al , 2005bSchmidt et al 2007;Christensen-Dalsgaard and Gerdes 2008;Jørgensen et al 2009;Prysak et al 2009;Yamaguchi et al 2009;Zhang and Inouye 2009). RelE has been the most extensively characterized ribosome-dependent mRNA interferase.…”

Section: Discussionmentioning

confidence: 99%

Escherichia coli rnlA and rnlB Compose a Novel Toxin–Antitoxin System

Koga

Otsuka

Lemire³

et al. 2011

Genetics

142

163

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RNase LS was originally identified as a potential antagonist of bacteriophage T4 infection. When T4 dmd is defective, RNase LS activity rapidly increases after T4 infection and cleaves T4 mRNAs to antagonize T4 reproduction. Here we show that rnlA, a structural gene of RNase LS, encodes a novel toxin, and that rnlB (formally yfjO), located immediately downstream of rnlA, encodes an antitoxin against RnlA. Ectopic expression of RnlA caused inhibition of cell growth and rapid degradation of mRNAs in DrnlAB cells. On the other hand, RnlB neutralized these RnlA effects. Furthermore, overexpression of RnlB in wild-type cells could completely suppress the growth defect of a T4 dmd mutant, that is, excess RnlB inhibited RNase LS activity. Pull-down analysis showed a specific interaction between RnlA and RnlB. Compared to RnlA, RnlB was extremely unstable, being degraded by ClpXP and Lon proteases, and this instability may increase RNase LS activity after T4 infection. All of these results suggested that rnlA-rnlB define a new toxin-antitoxin (TA) system. B ACTERIAL toxin-antitoxin (TA) systems are composed of a stable toxin and an unstable antitoxin (reviewed in Engelberg-Kulka and Glaser 1999). There are two different types of TA systems depending on the nature of antitoxin. In the type I systems, antitoxin is a small regulatory RNA that blocks the translation of toxin (Gerdes and Wagner 2007). In the type II systems, both toxin and antitoxin are proteins and antitoxin neutralizes toxin by direct interaction (Zhang et al. 2003a). When expression from type II TA loci is impaired by various kinds of stresses, such as amino acid starvation or translational inhibition by antibiotics (Christensen et al. 2001;Sat et al. 2001), antitoxin is rapidly decreased and consequently the level of toxin unbound (UB) with antitoxin is increased, leading to the activation of toxin (reviewed in Gerdes et al. 2005).RNase LS contributes to mRNA turnover in Escherichia coli, although its effect seems modest in comparison to that of a major RNase, RNase E (Otsuka and Yonesaki 2005). Recently we found one important role for this RNase in the physiology of E. coli cells: it targets cyaA mRNA (encoding adenylate cyclase) to reduce its expression (Iwamoto et al. 2008). Interestingly, the activity of RNase LS becomes much stronger after T4 infection ( We surveyed the E. coli DNA sequence in the vicinity of rnlA and found a promoter-like sequence, the open reading frame (ORF) of rnlA, the ORF of the downstream gene rnlB (formerly yfjO), and a terminator-like sequence consistently aligned in this order, suggesting that rnlA and rnlB form an operon. In addition, the terminal region in the rnlA ORF and the start region of the rnlB ORF overlap by 7 bp, implying an intimate coupling in their expression. These features prompted us to inquire whether rnlB is involved in RNase LS activity. In this study, we demonstrate that RnlB suppresses RNase LS activity. We also demonstrated that expression of RnlA in the absence of RnlB degrades E. coli bulk ...

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“…It has been shown that, in many cases, the unfolded nature of the antitoxin protein or its unstructured C-terminal domain is the cause of its vulnerability to degradation by intracellular proteases. In most cases, the Lon protease, which represents a major class of ATP-dependent proteases, is involved in antitoxin degradation (2)(3)(4)(5)(6)(7)(8)(9)(10). There are also known TA systems that use the two-component protease ClpP, which cooperates with the ATPase-active chaperones ClpA or ClpX (11,12).…”

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confidence: 99%