Mechanism of killer gene activation. Antisense RNA-dependent RNase III cleavage ensures rapid turn-over of the stable Hok, SrnB and PndA effector messenger RNAs

Gerdes, Kenn; Nielsen, Allan K.; Thorsted, Peter; Wagner, E. Gerhart H.

doi:10.1016/0022-2836(92)90621-p

Cited by 116 publications

(94 citation statements)

References 26 publications

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“…It was found that the hok mRNA is processed at the 3Ј end (22) and upon truncation folds into a new structure in which the binding sites for the Sok RNA and the ribosome are more accessible (14,35). Once formed, the hok mRNA-Sok RNA duplex is subject to cleavage by RNase III, thus ensuring that hok cannot be translated (19). The relative stabilities of both the hok mRNA and Sok RNA are another important aspect of the regulation.…”

Section: Processing and Block In Translation Of An Overlapping Open Rmentioning

confidence: 99%

Small Toxic Proteins and the Antisense RNAs That Repress Them

Fozo

Hemm

Storz

2008

Microbiol Mol Biol Rev

224

235

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SUMMARY There has been a great expansion in the number of small regulatory RNAs identified in bacteria. Some of these small RNAs repress the synthesis of potentially toxic proteins. Generally the toxin proteins are hydrophobic and less than 60 amino acids in length, and the corresponding antitoxin small RNA genes are antisense to the toxin genes or share long stretches of complementarity with the target mRNAs. Given their short length, only a limited number of these type I toxin-antitoxin loci have been identified, but it is predicted that many remain to be found. Already their characterization has given insights into regulation by small RNAs, has suggested functions for the small toxic proteins at the cell membrane, and has led to practical applications for some of the type I toxin-antitoxin loci.

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Section: Processing and Block In Translation Of An Overlapping Open Rmentioning

confidence: 99%

Small Toxic Proteins and the Antisense RNAs That Repress Them

Fozo

Hemm

Storz

2008

Microbiol Mol Biol Rev

224

235

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“…It encodes a highly potent host killing (Hok) toxin, and an antisense RNA antitoxin, suppression of killing (Sok). The Sok antisense RNA regulates the expression of the hok mRNA by binding to the hok mRNA and initiating RNase III decay of the duplex, thereby inhibiting the translation of the hok transcript [2,3]. However, in daughter cells that have lost the plasmid, the acquired Sok RNA are more rapidly degraded than the hok mRNA, thereby releasing the more stable hok mRNA for translation and subsequent cell death by the toxin produced.…”

Section: Introductionmentioning

confidence: 99%

The role of the hok/sok locus in bacterial response to stressful growth conditions

Chukwudi

Good

2015

Microbial Pathogenesis

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“…All elements of the model depicted in figure 3b were verified experimentally [52,60,61,65]. A metastable hairpin forms in the nascent transcript at the very 5 0 -end of hok mRNA (figure 3b(i)) and persists until the mRNA 5 0 -end pairs with the mRNA 3 0 -end in the full-length (FL) mRNA to form a highly folded, stable structure ( figure 3b(ii)).…”

Section: Complex Regulation Of the Hok/sok Module Of Plasmid R1mentioning

confidence: 83%

“…After the initial interaction, the two fully complementary RNAs refold into very stable, complete duplexes that are rapidly and irreversibly cleaved by RNase III [59]. We showed that hok and Sok-RNA also form a duplex that is cleaved by RNase III [60,61]. This clear observation posed a conundrum: how can an mRNA whose translation is irreversibly inhibited by a cis-acting antisense RNA become activated in plasmid-free cells?…”

Section: Complex Regulation Of the Hok/sok Module Of Plasmid R1mentioning

confidence: 93%

Hypothesis: type I toxin–antitoxin genes enter the persistence field—a feedback mechanism explaining membrane homoeostasis

Gerdes

2016

Phil. Trans. R. Soc. B

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Bacteria form persisters, cells that are tolerant to multiple antibiotics and other types of environmental stress. Persister formation can be induced either stochastically in single cells of a growing bacterial ensemble, or by environmental stresses, such as nutrient starvation, in a subpopulation of cells. In many cases, the molecular mechanisms underlying persistence are still unknown. However, there is growing evidence that, in enterobacteria, both stochastically and environmentally induced persistence are controlled by the second messenger (p)ppGpp. For example, the ‘alarmone’ (p)ppGpp activates Lon, which, in turn, activates type II toxin–antitoxin (TA) modules to thereby induce persistence. Recently, it has been shown that a type I TA module, hokB / sokB , also can induce persistence. In this case, the underlying mechanism depends on the universally conserved GTPase Obg and, surprisingly, also (p)ppGpp. In the presence of (p)ppGpp, Obg stimulates hokB transcription and induces persistence. HokB toxin expression is under both negative and positive control: SokB antisense RNA inhibits hokB mRNA translation, while (p)ppGpp and Obg together stimulate hokB transcription. HokB is a small toxic membrane protein that, when produced in modest amounts, leads to membrane depolarization, cell stasis and persistence. By contrast, overexpression of HokB disrupts the membrane potential and kills the cell. These observations raise the question of how expression of HokB is regulated. Here, I propose a homoeostatic control mechanism that couples HokB expression to the membrane-bound RNase E that degrades and inactivates SokB antisense RNA. This article is part of the themed issue ‘The new bacteriology’.

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Mechanism of killer gene activation. Antisense RNA-dependent RNase III cleavage ensures rapid turn-over of the stable Hok, SrnB and PndA effector messenger RNAs

Cited by 116 publications

References 26 publications

Small Toxic Proteins and the Antisense RNAs That Repress Them

Small Toxic Proteins and the Antisense RNAs That Repress Them

The role of the hok/sok locus in bacterial response to stressful growth conditions

Hypothesis: type I toxin–antitoxin genes enter the persistence field—a feedback mechanism explaining membrane homoeostasis

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