Escherichia coli str. K-12 substr. MG1655 Transcriptome or Gene expression

Toxin-antitoxin (TA) systems are strongly implicated in the down-regulation of cell growth associated with stress survival and latent tuberculosis infection, yet the molecular underpinnings of this association are unknown because the activities and intracellular targets of these TA toxins are largely uncharacterized. We used a specialized RNA-seq approach to identify targets of a Mycobacterium tuberculosis VapC TA toxin, VapC-mt4 (also known as VapC4), that have eluded detection using conventional approaches. Distinct from the one other characterized VapC toxin in M. tuberculosis that cuts 23S rRNA at the sarcin-ricin loop, VapC-mt4 selectively targets three of the 45 M. tuberculosis tRNAs (tRNAAla2, tRNASer26 and tRNASer24) for cleavage at, or adjacent to, their anticodons resulting in the generation of tRNA halves. While tRNA cleavage is sometimes enlisted as a bacterial host defense mechanism, VapC-mt4 instead alters specific tRNAs to inhibit translation and modulate growth. This stress-linked activity of VapC-mt4 mirrors basic features of eukaryotic tRNases that also generate tRNA halves and inhibit translation in response to stress.