Abstract
Protein translation is the most common target of toxin-antitoxin system (TA) toxins. Sequence-specific endoribonucleases digest RNA in a sequence-specific manner, thereby blocking translation. While past studies mainly focused on the digestion of mRNA, recent analysis revealed that toxins can also digest tRNA, rRNA and tmRNA. Purified toxins can digest single-stranded portions of RNA containing recognition sequences in the absence of ribosome in vitro. However, increasing evidence suggests that in vivo digestion may occur in association with ribosomes. Despite the prevalence of recognition sequences in many mRNA, preferential digestion seems to occur at specific positions within mRNA and also in certain reading frames. In this review, a variety of tools utilized to study the nuclease activities of toxins over the past 15 years will be reviewed. A recent adaptation of an RNA-seq-based technique to analyze entire sets of cellular RNA will be introduced with an emphasis on its strength in identifying novel targets and redefining recognition sequences. The differences in biochemical properties and postulated physiological roles will also be discussed.
Highlights
Toxin-antitoxin (TA) systems are ubiquitous modules found in almost all sequenced bacterial genomes [1,2]
Toxin activity is blocked by antitoxins when approximately an equivalent amount of toxin and antitoxin is present in a cell
Lowering the antitoxin concentration allows for the increase in free toxins, which leads to the arrest of cell growth
Summary
Toxin-antitoxin (TA) systems are ubiquitous modules found in almost all sequenced bacterial genomes [1,2]. In type V TA systems, the antitoxin is a nuclease that digests toxin mRNA to repress expression [10]. While earlier in vivo digestion studies of sequence-specific ribonucleases were mainly focused on the digestion of mRNA, recent studies have shown that some toxins can digest other types of RNA, such as rRNA, tRNA, sRNA and tmRNA [2,4,24,25,26,32,35]. Various homologues of ribonucleases will be introduced with a focus on sequence specificity and the types of RNA substrates 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. *1 Single base in UA can be changed to another base; *2 with 1 or 2 base alterations; *3 additional cleavage sites with higher concentrations of enzymes; *4 cleavage occurs at 50 and/or 30 side of the G-residue
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