Characterization of mRNA interferases from Mycobacterium tuberculosis

Ling Zhu, Yonglong Zhang, Jiah Shin Teh, Junjie Zhang, Nancy Connell, Harvey Rubin, Masayori Inouye

Research output: Contribution to journalArticle

Abstract

mRNA interferases are sequence-specific endoribonucleases encoded by the toxin-antitoxin systems in the bacterial genomes. MazF from Escherichia coli has been shown to be an mRNA interferase that specifically cleaves at ACA sequences in single-stranded RNAs. It has been shown that MazF induction in E. coli effectively inhibits protein synthesis leading to cell growth arrest in the quasidormant state. Here we have demonstrated that Mycobacterium tuberculosis contains at least seven genes encoding MazF homologues (MazF-mt1 to -mt7), four of which (MazF-mt1, -mt3, -mt4, and -mt6) caused cell growth arrest when induced in E. coli. MazF-mt1 and MazF-mt6 were purified and characterized for their mRNA interferase specificities. We showed that MazF-mt1 preferentially cleaves the era mRNA between U and A in UAC triplet sequences, whereas MazF-mt6 preferentially cleaves U-rich regions in the era mRNA both in vivo and in vitro. These results indicate that M. tuberculosis contains sequence-specific mRNA interferases, which may play a role in the persistent dormancy of this devastating pathogen in human tissues.

Original languageEnglish (US)
Pages (from-to)18638-18643
Number of pages6
JournalJournal of Biological Chemistry
Volume281
Issue number27
DOIs
StatePublished - Jul 7 2006

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Zhu, L., Zhang, Y., Teh, J. S., Zhang, J., Connell, N., Rubin, H., & Inouye, M. (2006). Characterization of mRNA interferases from Mycobacterium tuberculosis. Journal of Biological Chemistry, 281(27), 18638-18643. https://doi.org/10.1074/jbc.M512693200