MazF cleaves cellular mRNAs specifically at ACA to block protein synthesis in Escherichia coli.
Escherichia coli contains operons called "addiction modules," encoding toxin and antitoxin, which are responsible for growth arrest and cell death. Here, we demonstrate that MazF toxin encoded by "mazEF addiction module" is a sequence-specific (ACA) endoribonuclease functional only for single-stranded RNA. MazF works as a ribonuclease independent of ribosomes, and is, therefore, functionally distinct from RelE, another E. coli toxin, which assists mRNA cleavage at the A site on ribosomes. Upon induction, MazF cleaves whole cellular mRNAs to efficiently block protein synthesis. Purified MazF inhibited protein synthesis in both prokaryotic and eukaryotic cell-free systems. This inhibition was released by MazE, the labile antitoxin against MazF. Thus, MazF functions as a toxic endoribonuclease to interfere with the function of cellular mRNAs by cleaving them at specific sequences leading to rapid cell growth arrest and cell death. The role of such endoribonucleases may have broad implication in cell physiology under various growth conditions.
Department of Biochemistry, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.
Yonglong
Y
Zhang
Junjie
J
Zhang
Klaus P
KP
Hoeflich
Mitsuhiko
M
Ikura
Guoliang
G
Qing
Masayori
M
Inouye
D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D001427:Bacterial Toxins / Q000378:metabolism*; D001483:Base Sequence / Q000187:drug effects / Q000235:genetics; D016923:Cell Death / Q000502:physiology; D002474:Cell-Free System / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D011500:Protein Synthesis Inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C422954:MazE protein, E coli; C422955:MazF protein, E coli; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D004722:Endoribonucleases