# Toxins of Prokaryotic Toxin-Antitoxin Systems with Sequence-Specific Endoribonuclease Activity
## 1 Introduction
MazF-ec cleaves 16S rRNA, producing stress ribosomes that specifically translate leader-less mRNAs [32]. A homologue of MazF in _Mycobacterium tuberculosis_, MazF-mt3, cleaves the helix/loop 70 of 23S rRNA and the anti-Shing-Dalgarno (aSD) sequence of 16S rRNA, which also appears to allow a selective translation of leaderless mRNA in _Mycobacterium_[26]. The digestion of 23S rRNA at the single-stranded region of helix/loop 70 is also catalyzed by another MazF homologue in _M. tuberculosis_, MazF-mt6 [24]. A phylogenetically unrelated ribonuclease, VapC, can digest 23S rRNA, but it cleaves a separate region of the 23S rRNA, the sarcin-ricin loop [36]. In addition, VapC from _Shigella flexueri_ 2a and MazF-mt9 of _M. tuberculosis_ digest tRNA in a sequence- and likely in a structure-dependent manner [25; 35]. It is interesting to note that unlike the digestion of mRNA, the digestion of tRNA and rRNA occurs primarily at one or two sites [24; 25; 26; 26; 32; 35]. In _E. coli_, two major stable digestion products of 16S rRNA were detected following incubation with MazF [37]. Furthermore, the authors have shown that these digested 16S rRNA products are stable in vivo and can be reverted back to a full size, functional unit by RNA ligase (RtcB) [37]. The reversibility of rRNA cleavage must be included in future studies of the toxin's control of translation. In Type II TA systems, antitoxin proteins bind their own promoter region and inhibit transcription [38; 39]. Toxin and antitoxin proteins form a complex, which can also function as a transcriptional repressor. In many TA systems, the strength of binding between the DNA and TA complex differs based on the stoichiometric ratio of toxins and antitoxins, exhibiting conditional cooperativity [40]. Transcription is strongly inhibited at intermediate toxin/antitoxin ratios, while transcription is allowed at both high and low ratios. As some TA systems can regulate the transcription of genes other than their own, altering concentrations of toxin and/or antitoxin seems to have an effect on global gene expression patterns [41; 42]. The scope of this review is to summarize the biochemical properties of known TA toxins with sequence-specific ribonuclease activities. It should be noted that toxins with such activities thus far are classified as Type II or III TA systems (Table 1), but not all Type II and III toxins are nucleases. Various homologues of ribonucleases will be introduced with a focus on sequence specificity and the types of RNA substrates. Furthermore, their roles in bacterial physiology, either caused directly by the digestion of RNA or by altering transcriptional regulatory activities of TA complexes, will be discussed. \begin{table}
\begin{tabular}{c c c c c c c} \hline \hline \multirow{2}{*}{**Toxins**} & \multirow{2}{*}{**Types**} & \multirow{2}{*}{**Sources**} & \multirow{2}{*}{**Consensus Sequences**} & \multicolumn{4}{c}{**Substrates**} \\ \cline{5-8}  & & & **(Reference)** & & **mRNA** & **rRNA** & **tRNA** & **tmRNA** \\ \hline \hline \multicolumn{8}{l}{MazF-CbrpBK} \\ \hline \hline \multicolumn{8}{l}{MazF-ec} \\ \hline \hline \multicolumn{8}{l}{ChpBK} \\ \hline \hline \multirow{2}{*}{Kid (PemK)} & \multirow{2}{*}{ \begin{tabular}{c} _E. coli_ \\ _E. coli_ \\ \end{tabular}  } & \multirow{2}{*}{ \begin{tabular}{c} _A’CA_[3] \\ _E. coli_ \\ \end{tabular}  } & \multirow{2}{*}{\ \begin{tabular}{c} + \\ _E. coli_ \\ \end{tabular}  } & \multirow{2}{*}{
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