Mycobacterium tuberculosis VapC4 toxin engages small ORFs to initiate an integrated oxidative and copper stress response.

ABSTRACT: The Mycobacterium tuberculosis (Mtb) VapBC4 toxin-antitoxin system is essential for the establishment of Mtb infection. Using a multitier, systems-level approach, we uncovered the sequential molecular events triggered by the VapC4 toxin that activate a circumscribed set of critical stress survival pathways which undoubtedly underlie Mtb virulence. VapC4 exclusively inactivated the sole transfer RNA^Cys (tRNA^Cys) through cleavage at a single site within the anticodon sequence. Depletion of the pool of tRNA^Cys led to ribosome stalling at Cys codons within actively translating messenger RNAs. Genome mapping of these Cys-stalled ribosomes unexpectedly uncovered several unannotated Cys-containing open reading frames (ORFs). Four of these are small ORFs (sO

SUBMITTER: Barth VC 

PROVIDER: S-EPMC8364209 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature