Cloaked dagger: tRNA slicing by an unlikely culprit

The unusually high number of toxin-antitoxin (TA) systems in Mycobacterium tuberculosis, the etiological agent of tuberculosis, is thought to contribute to the unique ability of this pathogen to evade killing by the immune system and persist as a latent infection. One TA family, designated mazEF (for the MazE antitoxin and MazF toxin), comprises 10 of the >80 TA systems in the M. tuberculosis genome. Here we discuss the significance of our recent Nucleic Acids Res. paper that reports a surprising enzymatic activity for the MazF-mt9 toxin-sequence- and structure-specific cleavage of tRNA to generate tRNA halves-that underlies the growth-regulating properties of this toxin. This activity is distinct from all characterized MazF family members in M. tuberculosis and other bacteria; instead it is strikingly similar to that documented for members of another toxin family, VapC, despite the absence of sequence or structural similarity.