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.
Highlights
Most bacteria contain “suicidal” or “toxic” genes whose expression leads to growth arrest and eventual death upon exposure to stress
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
In view of the quasidormancy caused by MazF induction in E. coli, our results suggest that multiple mRNA interferases in M. tuberculosis may play a role in the multidimensional dormancy of this pathogen in human tissues
Summary
We showed that MazF-mt preferentially cleaves the era mRNA between U and A in UAC triplet sequences, whereas MazF-mt 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. MazF-induced cells are capable of synthesizing a protein, if the gene encoding this protein is devoid of ACA sequences [4] This metabolically active dormant state caused by mRNA interferase induction is called “quasidormancy” [4] and has important implications in the physiology of various pathogenic bacteria, including persistent multidrug resistance. In view of the quasidormancy caused by MazF induction in E. coli, our results suggest that multiple mRNA interferases in M. tuberculosis may play a role in the multidimensional dormancy of this pathogen in human tissues
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