{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T18:31:40Z","timestamp":1793298700700,"version":"4.5.0"},"reference-count":48,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,5,21]]},"abstract":"<jats:p>\n                    The\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    genome contains an unusually high number of toxin\u2013antitoxin modules, some of which have been suggested to play a role in the establishment and maintenance of latent tuberculosis. Nine of these toxin\u2013antitoxin loci belong to the\n                    <jats:italic>mazEF<\/jats:italic>\n                    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 \u201cmRNA interferases.\u201d Here we demonstrate that a MazF family member from\n                    <jats:italic>M. tuberculosis,<\/jats:italic>\n                    MazF-mt6, has an additional role\u2014inhibiting translation through targeted cleavage of 23S rRNA in the evolutionarily conserved helix\/loop 70. We first determined that MazF-mt6 cleaves mRNA at\n                    <jats:sup>5<\/jats:sup>\n                    <jats:sup>\u2032<\/jats:sup>\n                    UU\u2193CCU\n                    <jats:sup>3\u2032<\/jats:sup>\n                    sequences. We then discovered that MazF-mt6 also cleaves\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    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\u2013mediated 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\u201330S 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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1222031110","type":"journal-article","created":{"date-parts":[[2013,5,7]],"date-time":"2013-05-07T00:00:47Z","timestamp":1367884847000},"page":"8501-8506","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":135,"title":["Mycobacterial toxin MazF-mt6 inhibits translation through cleavage of 23S rRNA at the ribosomal A site"],"prefix":"10.1073","volume":"110","author":[{"given":"Jason M.","family":"Schifano","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School at Rutgers University, Piscataway, NJ 08854;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Edifor","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Children\u2019s Hospital Boston, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared D.","family":"Sharp","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School at Rutgers University, Piscataway, NJ 08854;"},{"name":"Division of Infectious Diseases, Children\u2019s Hospital Boston, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Computer Engineering and Computer Science Department, University of Louisville, Louisville, KY 40292"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvind","family":"Konkimalla","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School at Rutgers University, Piscataway, NJ 08854;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert N.","family":"Husson","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Children\u2019s Hospital Boston, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy A.","family":"Woychik","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Robert Wood Johnson Medical School at Rutgers University, Piscataway, NJ 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