The mRNA interferases, MazF-mt3 and MazF-mt7 from Mycobacterium tuberculosis target unique pentad sequences in single-stranded RNA

Ling Zhu, Sangita Phadtare, Hirofumi Nariya, Ming Ouyang, Robert N. Husson, Masayori Inouye

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

mRNA interferases are sequence-specific endoribonucleases encoded by toxin-antitoxin (TA) systems in bacterial genomes. Previously, we demonstrated that Mycobacterium tuberculosis contains at least seven genes encoding MazF homologues (MazF-mt1 to -mt7) and determined cleavage specificities for MazF-mt1 and MazF-mt6. Here we have developed a new general method for the determination of recognition sequences longer than three bases for mRNA interferases with the use of phage MS2 RNA as a substrate and CspA, an RNA chaperone, which prevents the formation of secondary structures in the RNA substrate. Using this method, we determined that MazF-mt3 cleaves RNA at UǓCCU or CǓCCU and MazF-mt7 at ǓCGCU (̌indicates the cleavage site). As pentad sequence recognition is more specific than those of previously characterized mRNA interferases, bioinformatics analysis was carried out to identify M. tuberculosis mRNAs that may be resistant to MazF-mt3 and MazF-mt7 cleavage. The pentad sequence was found to be significantly underrepresented in several genes, including members of the PE and PPE families, large families of proteins that play a role in tuberculosis immunity and pathogenesis. These data suggest that MazF-mt3 and MazF-mt7 or other mRNA interferases that target longer RNA sequences may alter protein expression through differential mRNA degradation, a regulatory mechanism that may allow adaptation to environmental conditions, including those encountered by pathogens such as M. tuberculosis during infection.

Original languageEnglish (US)
Pages (from-to)559-569
Number of pages11
JournalMolecular Microbiology
Volume69
Issue number3
DOIs
StatePublished - Aug 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Molecular Biology

Fingerprint

Dive into the research topics of 'The mRNA interferases, MazF-mt3 and MazF-mt7 from Mycobacterium tuberculosis target unique pentad sequences in single-stranded RNA'. Together they form a unique fingerprint.

Cite this