The study of bacteriophages (phages) and prophages has provided key insights into almost every cellular process as well as led to the discovery of unexpected new mechanisms and the development of valuable tools. This is exemplified for RNA-based regulation. For instance, the characterization and exploitation of the anti-phage CRISPR systems is revolutionizing molecular biology. Phage-encoded proteins such as the RNA binding MS2 protein, which is broadly used to isolate tagged RNAs, also have been developed as valuable tools. Hfq, the RNA chaperone protein central to the function of many base pairing small RNAs (sRNAs), was first characterized as a bacterial host factor required for Qβ phage replication. The ongoing studies of RNAs are continuing to reveal regulatory connections between infecting phages, prophages and bacteria and to provide novel insights. There are bacterial and prophage sRNAs that regulate prophage genes, which impact bacterial virulence as well as bacterial cell killing. Conversely, phage- and prophage-encoded sRNAs modulate the expression of bacterial genes modifying metabolism. An interesting subcategory of the prophage-encoded sRNAs are sponge RNAs that inhibit the activities of bacterial-encoded sRNAs. Phages also affect post-transcriptional regulation in bacteria through proteins that inhibit or alter the activities of key bacterial proteins involved in posttranscriptional regulation. However, what is most exciting about phage and prophage research, given the millions of phage-encoded genes that have not yet been characterized, is the vast potential for discovering new RNA regulators and novel mechanisms and for gaining insight into the evolution of regulatory RNAs
