Vesper, O., Amitai, S., Belitsky, M., Byrgazov, K., Kaberdina, A., Engelberg-Kulka, H., & Moll, I. (2011). Selective Translation of Leaderless mRNAs by Specialized Ribosomes Generated by MazF in Escherichia coli Cell, 147 (1), 147-157 DOI: 10.1016/j.cell.2011.07.047
This paper has characterised an interesting new mechanism of stress adaptation in bacteria in which ribosomes are modified to selectively translate a subset of mRNAs that have also been modified by the same enzyme.
Toxin-antitoxin (TA) modules are widespread prokaryotic genetic elements that have generally been characterised as selfish DNA when encoded on plasmids. Chromosomally located TA systems functions are more likely to be integrated into the host cells regulatory networks. mazEF is a well characterised chromosomal TA system in E.coli. The two genes are cotranscribed as an operon; mazE encoding a relatively labile antitoxin that inactivates the more stable endoribonuclease MazF. Under conditions of cell stress mazEF expression is inhibited. As MazE is less stable and degraded by a protease, MazF activity is released. MazF cleaves single stranded mRNAs at ACA sequences hence inhibiting protein synthesis. However this inhibition is not global: about 10% of protein’s synthesis are specifically enabled by MazF action. Some of these protein’s actions are responsible for programmed cell death, others have been shown to permit the survival of a subpopulation of bacterial cells (Amitai et al.2009). This new paper has uncovered the mechanism by which the selective synthesis of this subset of the cell’s proteins is activated by MazF.
Analysing transcripts encoding proteins known to be synthesised in the presence of MazF activity the authors found that they were cleaved at ACA sequences at or closely upstream of their AUG translation start sites. This creates a population of leaderless mRNAs (lmRNAs) that the paper also shows are selectively translated in the presence of MazF activity. Postulating that the selective translation of lmRNAs could be mediated by MazF modifications to the ribosome itself, the investigators went on to show that MazF also cleaves the 16S rRNA of the 30S ribosomal subunit. This cleavage results in the loss of 43nt from the 3′ end of the 16S rRNA including the anti-Shine Dalgarno sequence (aSD). SD – aSD interactions are important for the initiation of translation of canonical mRNAs with structured 5′ UTRs. However, in this case MazF generates specialised “Stress Ribosomes” lacking the aSD that selectively translate a “leaderless mRNA regulon” also generated by cleavage by MazF.
This paper is important and interesting in that it has discovered an elegant and novel molecular mechanism employed by bacteria during times of environmental stress. It also adds greatly to understanding bacterial programmed cell death and the functions of chromosomally located TA systems both of which are contentious subjects in relation to how their evolution typifies aspects of both altruism and selfishness.