Bacteriophage-encoded 24B_1 molecule resembles herpesviral microRNAs and plays a crucial role in the development of both the virus and its host.

The 24B_1 small non-coding RNA molecule has been identified in Escherichia coli after induction of Shiga toxin-converting bacteriophage Φ24B. In this work, we focused on its direct role during phage and bacterial host development. We observed that in many aspects, this phage sRNA resembles herpesviral microRNAs. Similar to microRNAs, the mature 24B_1 is a short molecule, consisting of just 20 nucleotides. It is generated by cleaving the 80-nt long precursor transcript, and likely it undergoes a multi-step maturation process in which the Hfq protein plays an important role, as confirmed by demonstration of its binding to the 24B_1 precursor, but not to the 24B_1 mature form. Moreover, 24B_1 plays a significant role in maintaining the prophage state and reprogramming the host's energy metabolism. We proved that overproduction of this molecule causes the opposite physiological effects to the mutant devoid of the 24B_1 gene, and thus, favors the lysogenic pathway. Furthermore, the 24B_1 overrepresentation significantly increases the efficiency of expression of phage genes coding for proteins CI, CII, and CIII which are engaged in the maintenance of the prophage. It seems that through binding to mRNA of the sdhB gene, coding for the succinate dehydrogenase subunit, the 24B_1 alters the central carbon metabolism and causes a drop in the ATP intracellular level. Interestingly, a similar effect, called the Warburg switch, is caused by herpesviral microRNAs and it is observed in cancer cells. The advantage of the Warburg effect is still unclear, however, it was proposed that the metabolism of cancer cells, and all rapidly dividing cells, is adopted to convert nutrients such as glucose and glutamine faster and more efficiently into biomass. The availability of essential building blocks, such as nucleotides, amino acids, and lipids, is crucial for effective cell proliferation which in turn is essential for the prophage and its host to stay in the lysogenic state.