Laboratory of Molecular Biology and Group for Higher Education
- Professor
- Tetsuro YONESAKI
yonesaki@bio.sci.osaka-u.ac.jp - Assistant Professor
- Yuichi OTSUKA
otsukay@bio.sci.osaka-u.ac.jp 
Animal Science
Biological Sciences
Natural Science Main Building, Toyonaka Campus
Research Theme
Bacteriophage (Phage) infecting prokaryote occupies the largest biomass on the Earth. Prokaryote corresponds to the lowest level of a food chain and because phage strongly affects a density of bacterial cells, it has an important role in the ecosystem of the Earth. Prokaryote has changed its outer surface to escape from phage-infection or has developed mechanisms such as restriction enzymes or CRISPR to interfere with phage growth. On the other hand, phage has developed mechanisms to overcome the anti-phage mechanisms. Accordingly, phage and prokaryote are in the process of coevolution, in which a respective tactics has a role in evolution of the other.
Toxin-antitoxin as an anti-phage mechanism
Prokaryote has TA (toxin-antitoxin) systems to respond to various stresses. In general, toxins are stable and antitoxins are unstable. Accordingly, when the gene expression of a TA system is impaired by stress, the antitoxin disappears. Consequently, the toxin is activated to repress cell growth or to cause cell death when stress is not tolerable (Fig. 1). T4 is a phage to infect E. coli . E. coli cells have a TA system composed of RnlA and RnlB. T4 phage has a mechanism for quick shut-off of host gene expression. Thereby, extremely unstable RnlB (antitoxin) rapidly disappears after T4 phage infection. Released RnlA (toxin) plays a central role in RNase LS, which has an endoribonucleolytic activity. T4 has its own antitoxin against RnlA, called Dmd. Dmd is synthesized immediately after T4 infection and binds to RnlA instead of RnlB to block RNase LS acitivity that potentially inhibits T4 gene expression by rapid degradation of mRNA (Fig. 2). In fact, when a dmd mutant of T4 infects, it can not propagate in the presence of RnlA-RnlB.
Control of host mRNA degradation by T4 phage
Host mRNAs are rapidly degraded immediately after T4 infection. This mechanism is considered to support T4 propagation by providing ribonucleotides required for efficient transcription of T4 genes and by releasing ribosomes for translation of T4 genes. The rapid degradation of host mRNAs is mainly promoted by host RNase E. Therefore, T4 should have a mechanism for activation of RNase E.
A TA system consists of a pair of contiguous genes. A toxin has an activity to block cell growth or to cause cell death. An antitoxin directly binds to a toxin and inactivates its activity. In general, a toxin is stable, whereas an antitoxin is unstable because of protease attack. When gene expression is impaired by stress, an antitoxin is degraded, causing release of toxin.
Bibliography
Otsuka, Y. and Yonesaki, T. Dmd of bacteriophage T4 functions as an antitoxin against Escherichia coli LsoA and RnlA toxins. Mol. Microbiol. 83 , 669 - 681 (2012)
Koga, M., Otsuka, Y., Lemire, S., and Yonesaki, T. Escherichia coli rnlA and rnlB compose a novel toxin-antitoxin system. Genetics 187 , 123 - 130 (2011)
Otsuka Y., Miki K., Koga M., Katayama N., Morimoto W., Takahashi Y., Yonesaki T. IscR regulates RNase LS activity by repressing rnlA transcription. Genetics 185 , 823 - 830 (2010)
Otsuka Y, Kedersha NL, Schoenberg DR. Identification of a cytoplasmic complex that adds a cap onto 5'-monophosphate RNA Mol Cell Biol. 29 , 2155 - 2167 (2009)
Iwamoto,A., Lemire, S. and Yonesaki, T. Post-transcriptional control of Crp-cAMP by RNase LS in Escherichia coli. Mol. Microbiol. 70 , 1570 - 1578 (2008)
Otsuka Y, Koga M, Iwamoto A, Yonesaki T A role of RnlA in the RNase LS activity from Escherichia coli. Genes Genet. Syst. 82 , 291 - 299 (2007)
Contact
Tetsuo Yonesaki
Department of Biological Sciences
Graduate School of Science
Osaka University
1-1 Machikaneyama-cho, Toyonaka
Osaka 560-0043, JAPAN
Tel +81-6-6850-5813
Fax +81-6-6850-6769
yonesaki@bio.sci.osaka-u.ac.jp