MazF, an mRNA Interferase, Mediates Programmed Cell Death During Multicellular Myxococcus Development

Cell. 2008 Jan 11;132(1):55-66. doi: 10.1016/j.cell.2007.11.044.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis / genetics*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Base Sequence
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Division / physiology
  • Cell Proliferation
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Endoribonucleases / genetics
  • Endoribonucleases / metabolism*
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism
  • Gene Deletion
  • Gene Expression Regulation, Bacterial / genetics
  • Molecular Sequence Data
  • Myxococcus / enzymology*
  • Myxococcus / genetics
  • Phosphorylation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Homology, Amino Acid
  • Spheroids, Cellular / cytology
  • Spheroids, Cellular / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic / genetics

Substances

  • Apoptosis Regulatory Proteins
  • Bacterial Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • MazF protein, E coli
  • MrpC protein, Myxococcus xanthus
  • RNA, Messenger
  • Transcription Factors
  • Endoribonucleases