Toxin-mediated ribosome stalling reprograms the Mycobacterium tuberculosis proteome.

ABSTRACT: Mycobacterium tuberculosis readily adapts to survive a wide range of assaults by modifying its physiology and establishing a latent tuberculosis (TB) infection. Here we report a sophisticated mode of regulation by a tRNA-cleaving toxin that enlists highly selective ribosome stalling to recalibrate the transcriptome and remodel the proteome. This toxin, MazF-mt9, exclusively inactivates one isoacceptor tRNA, tRNA^Lys43-UUU, through cleavage at a single site within its anticodon (UU↓U). Because wobble rules preclude compensation for loss of tRNA^Lys43-UUU by the second M. tuberculosis lysine tRNA, tRNA^Lys19-CUU, ribosome stalling occurs at in-frame cognate AAA Lys codons. Consequently, the transcripts harboring these stalled ribosomes are selectively cleaved by

SUBMITTER: Barth VC 

PROVIDER: S-EPMC6620280 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature