# Toxins of Prokaryotic Toxin-Antitoxin Systems with Sequence-Specific Endoribonuclease Activity
## 3 Physiological Roles
### Stress Response  
The gene expression of many TA systems can be altered under various stress conditions [122; 2; 123; 4]. For instance, antibiotics such as chloramphenicol, mitomycin C, kanamycin and ciprofloxacin activate the transcription of TA systems, including _mazEF_[124; 125; 126; 127; 128; 129]. Glucose starvation, chloramphenicol, as well as amino acid starvation induce _hicA_ expression [2]. Oxidative stress and ampicillin application induce _mqsRA_[126]. MqsRA is also implicated in deoxycholate tolerance [127].  
In particular, the role of MqsA in general stress responses has been well documented [96]. As a DNA binding protein, MqsA binds the promoter region of _rpoS_, as well as other promoters [39; 41]. RpoS is a stress-responsive alternative sigma factor, controlling approximately 500 genes in _E. coli_ in response to a variety of stresses [128]. MqsA is a negative regulator of _rpoS_ transcription, and deletion of _mqsA_ induces the expression of _rpoS_, which results in an increased stress resistance [96]. Conversely, overexpression of MqsA, both in wildtype and in _mqsRA_ deletion strains, lead to a decrease in oxidative stress, suggesting that MqsA affects stress resistance, independent of the toxin MqsR [96]. This effect is proposed to be mediated by affecting the expression of _rpoS_, as _rpoS_ controls the expression of catalase, an essential enzyme for oxidative stress response [96].  
Stringent response, caused by amino acid starvation, induces the expression of more than ten TA systems, including _mazEF_[122; 2; 4]. The exact role of TA ribonucleases in stringent responses is still under discussion. Although the digestion of cellular mRNA by induced toxins has been observed, [PERSON] and colleagues proposed that the majority of mRNA digestion is done by the stalled ribosomes [4]. TA toxin-mediated digestion may merely serve as an additional mechanism to further inhibit translation under extreme starvation conditions.  
VapBC6 of hyperthermophilic _Sulfolobus solftaricus_ is crucial for their thermophilicity [129]. When _vapBC6_ is deleted, cells become heat-sensitive, and the growth rate at elevated temperatures is reduced. The expression of the toxin VapC6 is induced at high temperatures, and its activity is temperature dependent. The enzyme shows full, partial and almost zero activity at 80 \({}^{\circ}\)C, 65 \({}^{\circ}\)C and 37 \({}^{\circ}\)C, respectively. A preferential in vivo degradation of a few gene transcripts (_ddpB-1_, _tetR_ and _vapB6_) by VapC6 has been detected, but its exact role in thermostability remains to be elucidated [129].  
As a DNA binding protein, PrIF controls the expression of the _prIF-yluaV_ operon [78]. The _prIF_ mutant allele (_prIF1_) was isolated as a suppressor of _ltrA_ (_degP_) null phenotype [130]. HtrA is a periplasmic protease that is essential for cell growth at higher temperatures [131]. The _prIF1_ loci also suppress the lethality caused by the clogging of SecYEG translocator with LamB-LacZ [132]. The activation of Lon is postulated to be important for these phenotypes. These results suggest the importance of _yhaV-prIF_ under stress conditions, particularly stress that induces ruinous membranes.  
The activation of HicA, YafQ and HigB suppresses the lethality caused by the loss of sigma E, an alternative sigma factor for extracytoplasmic stress response in _E. coli_[133]. The exact mechanism, however, remains unknown.