Cross-Regulation between Bacteria and Phages at a Posttranscriptional Level

Abstract

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.

The RNA–RNA interactome between a phage and its satellite virus reveals a small RNA that differentially regulates gene expression across both genomes

“…While many sRNAs have been shown to regulate various processes in V. cholerae (Hammer & Bassler, 2007; Peschek et al, 2020; Richard et al, 2010), less is known about sRNA regulation between MGEs, phages, and their host bacteria (Altuvia et al, 2018; Fröhlich & Papenfort, 2016). Both MGEs and prophages have been shown to use cis ‐ and trans ‐encoded sRNAs to regulate transcripts encoded on the core host genome, as well as on the MGEs themselves (Bloch et al, 2021; Tree et al, 2014; Wachter et al, 2018).…”

Non-genetic messenger RNA silencing reveals essential genes in phage-host interplay

“…It is also important to bear in mind that the ASOs used here were designed to translationally silence mRNAs, with the goal to suppress protein synthesis. However, there is a growing appreciation of noncoding RNA functions in phage-host interactions (Altuvia et al 2018, Sprenger et al 2024, and the ASO approach used here should be easily applicable to inhibiting phage-related regulatory small RNAs. Likewise, ASOs could be important for exploring the expanding class of minimal RNA replicators such as viroids and viroid-like covalently closed circular (ccc) RNAs, some of which are predicted to replicate in environmental bacteria (Lee et al 2023, Zheludev et al 2024.…”

Investigating the Prevalence of RNA-Binding Metabolic Enzymes in E. coli

“…By implication, the enrichment of corresponding mRNAs/asRNAs might give a hint that some of these genes of unknown function are involved in cell surface physiology in one way or another. While the phage mechanism of host-translational manipulation to promote selfproliferation is well-understood [88], implications of a possible specific posttranscriptional control of host cell surface genes are not described in the literature and comprise an intriguing matter to be explored.…”