{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Barth VC"],"funding":["HHS | National Institutes of Health","NIAID NIH HHS","Coordenação de Aperfeiçoamento de Pessoal de Nível Superior","new jersey commission on cancer research","NIH HHS"],"pagination":["e2022136118"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8364209"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["118(32)"],"pubmed_abstract":["The <i>Mycobacterium tuberculosis</i> (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<sup>Cys</sup> (tRNA<sup>Cys</sup>) through cleavage at a single site within the anticodon sequence. Depletion of the pool of tRNA<sup>Cys</sup> 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"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["<i>Mycobacterium tuberculosis</i> VapC4 toxin engages small ORFs to initiate an integrated oxidative and copper stress response."],"pmcid":["PMC8364209"],"funding_grant_id":["99999.013433/2013-00","DFHS18PPC045","R21 AI135461","S10 OD025140","AI135461","R01 AI154464","AI154464"],"pubmed_authors":["Husson RN","Barth VC","Woychik NA","Zheng H","Zeng J","Su X","Chauhan U"],"additional_accession":[]},"is_claimable":false,"name":"<i>Mycobacterium tuberculosis</i> VapC4 toxin engages small ORFs to initiate an integrated oxidative and copper stress response.","description":"The <i>Mycobacterium tuberculosis</i> (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<sup>Cys</sup> (tRNA<sup>Cys</sup>) through cleavage at a single site within the anticodon sequence. Depletion of the pool of tRNA<sup>Cys</sup> 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","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Aug","modification":"2026-05-08T10:35:22.292Z","creation":"2025-04-07T00:26:05.46Z"},"accession":"S-EPMC8364209","cross_references":{"pubmed":["34362841"],"doi":["10.1073/pnas.2022136118"]}}