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Characterization of mRNA interferases from Mycobacterium tuberculosis

Ling Zhu1, Yonglong Zhang, Jiah-Shin Teh

  • 1Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.

The Journal of Biological Chemistry
|April 14, 2006
PubMed

Insights

Mycobacterium tuberculosis possesses multiple MazF homologues, which are mRNA interferases. Four of these genes induced cell growth arrest in E. coli, suggesting a role in pathogen dormancy.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Bacterial Genetics

Background:

  • Toxin-antitoxin systems encode mRNA interferases, like MazF from Escherichia coli.
  • MazF enzymes are sequence-specific endoribonucleases that cleave single-stranded RNAs.
  • MazF induction in E. coli inhibits protein synthesis, causing cell growth arrest.

Purpose of the Study:

  • To investigate the presence and function of MazF homologues in Mycobacterium tuberculosis.
  • To characterize the mRNA cleavage specificities of M. tuberculosis MazF enzymes.

Main Methods:

  • Cloning and induction of M. tuberculosis MazF genes in E. coli.
  • Purification and biochemical characterization of MazF-mt1 and MazF-mt6.
  • In vitro and in vivo analysis of mRNA cleavage activity.

Main Results:

  • M. tuberculosis harbors at least seven MazF homologues.
  • Four M. tuberculosis MazF genes (MazF-mt1, -mt3, -mt4, -mt6) induced cell growth arrest in E. coli.
  • MazF-mt1 specifically cleaves at UAC sequences, while MazF-mt6 targets U-rich regions in era mRNA.

Conclusions:

  • M. tuberculosis possesses functional, sequence-specific mRNA interferases.
  • These MazF homologues may contribute to the persistent dormancy of M. tuberculosis in human tissues.

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