ArticleProceedings of the National Academy of Sciences of the United States of America2013
Mycobacterial toxin MazF-mt6 inhibits translation through cleavage of 23S rRNA at the ribosomal A site.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed.
- Ribosomal RNA cleavage by the previously unidentified RelS-RelI toxin-antitoxin system controls growth of Mycobacterium tuberculosis.Nucleic acids research · 2026Article
- The Pseudomonas aeruginosa ribonuclease Ribocin cleaves eukaryotic ribosomes at helix 69 to inhibit host translation.PLoS biology · 2026Article
- Systematic screening of archaeal MazF homologs reveals Tth-MazF1, a versatile, sequence-specific ribonuclease from Thermococcus thioreducens.Nucleic acids research · 2026Article
- Article
- Inhibition of Targeted Bacterial Growth Using MazF-Expressing Phagemids: A Novel Therapeutic Approach Based on Endoribonuclease Toxin Molecules.Microbiology and immunology · 2026Article
- Reversible dissociation of mitochondrial Complex V balances anabolic and energy-generating needs in cancer.iScience · 2026Article
- Key Proteins and Enzymatic Mechanisms Underlying Drug Resistance in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Ribonuclease toxin RelE1 inhibits growth of Mycobacterium tuberculosis through specific cleavage of the ribosomal anti-Shine-Dalgarno region.Nucleic acids research · 2025Article
- Deciphering the role of VapBC13 and VapBC26 toxin antitoxin systems in the pathophysiology of Mycobacterium tuberculosis.Communications biology · 2024Article
- Long Dynamic β1-β2 Loops inInternational journal of molecular sciences · 2024Article
- Mycobacterium tuberculosis strain with deletions in menT3 and menT4 is attenuated and confers protection in mice and guinea pigs.Nature communications · 2024Article
- Oxygen-Containing Quaternary Phosphonium Salts (oxy-QPSs): Synthesis, Properties, and Cellulose Dissolution.Polymers · 2023Article
- Structural and mutational analysis of MazE6-operator DNA complex provide insights into autoregulation of toxin-antitoxin systems.Communications biology · 2022Article
- Functional and Biochemical Characterization of the MazEF6 Toxin-Antitoxin System of Mycobacterium tuberculosis.Journal of bacteriology · 2022Article
- Combining cysteine scanning with chemical labeling to map protein-protein interactions and infer bound structure in an intrinsically disordered region.Frontiers in molecular biosciences · 2022Article
- Specialised ribosomes as versatile regulators of gene expression.RNA biology · 2022Review
- Photorhabdus antibacterial Rhs polymorphic toxin inhibits translation through ADP-ribosylation of 23S ribosomal RNA.Nucleic acids research · 2021Article
- Article
- Conserved Amino Acid Moieties ofFrontiers in microbiology · 2021Article
- PerSort Facilitates Characterization and Elimination of Persister Subpopulation in Mycobacteria.mSystems · 2020Article
23 more citing papers are in PubMed but not listed here.
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7 authors.
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Abstract
The Mycobacterium tuberculosis genome contains an unusually high number of toxin-antitoxin modules, some of which have been suggested to play a role in the establishment and maintenance of latent tuberculosis. Nine of these toxin-antitoxin loci belong to the mazEF family, encoding the intracellular toxin MazF and its antitoxin inhibitor MazE. Nearly every MazF ortholog recognizes a unique three- or five-base RNA sequence and cleaves mRNA. As a result, these toxins selectively target a subset of the transcriptome for degradation and are known as "mRNA interferases." Here we demonstrate that a MazF family member from M. tuberculosis, MazF-mt6, has an additional role--inhibiting translation through targeted cleavage of 23S rRNA in the evolutionarily conserved helix/loop 70. We first determined that MazF-mt6 cleaves mRNA at (5')UU↓CCU(3') sequences. We then discovered that MazF-mt6 also cleaves M. tuberculosis 23S rRNA at a single UUCCU in the ribosomal A site that contacts tRNA and ribosome recycling factor. To gain further mechanistic insight, we demonstrated that MazF-mt6-mediated cleavage of rRNA can inhibit protein synthesis in the absence of mRNA cleavage. Finally, consistent with the position of 23S rRNA cleavage, MazF-mt6 destabilized 50S-30S ribosomal subunit association. Collectively, these results show that MazF toxins do not universally act as mRNA interferases, because MazF-mt6 inhibits protein synthesis by cleaving 23S rRNA in the ribosome active center.
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