MazF, an mRNA interferase, mediates programmed cell death during multicellular Myxococcus development.
In prokaryotes, the toxin-antitoxin systems are thought to play important roles in growth regulation under stress conditions. In the E. coli MazE-MazF system, MazF toxin functions as an mRNA interferase cleaving mRNAs at ACA sequences to inhibit protein synthesis leading to cell growth arrest. Myxococcus xanthus is a bacterium displaying multicellular fruiting body development during which approximately 80% of cells undergo obligatory cell lysis. Here, we demonstrate that M. xanthus has a solitary mazF gene that lacks a cotranscribed antitoxin gene. The mazF deletion results in elimination of the obligatory cell death during development causing dramatic reduction in spore formation. Surprisingly, MrpC, a key developmental regulator, functions as a MazF antitoxin and a mazF transcription activator. Transcription of mrpC and mazF is negatively regulated via MrpC phosphorylation by a Ser/Thr kinase cascade. These findings reveal the regulated deployment of a toxin gene for developmental programmed cell death in bacteria.
Nariya
Hirofumi
H
Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
Inouye
Masayori
M
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D008969:Molecular Sequence Data; D016940:Myxococcus / Q000201:enzymology* / Q000235:genetics; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D018874:Spheroids, Cellular / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics
D051017:Apoptosis Regulatory Proteins; D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C422955:MazF protein, E coli; C433791:MrpC protein, Myxococcus xanthus; D012333:RNA, Messenger; D014157:Transcription Factors; D004722:Endoribonucleases