A large group of bacterial small regulatory RNAs (sRNAs) use the Hfq chaperone to mediate pairing with and regulation of mRNAs. Recent findings help to clarify how Hfq acts and highlight the role of the endonuclease RNase E and its associated proteins (the degradosome) in negative regulation by these sRNAs. sRNAs frequently uncouple transcription and translation by blocking ribosome access to the mRNA, allowing other proteins access to the mRNA. As more examples of sRNA-mediated regulation are studied, more variations on how Hfq, RNase E, and other proteins collaborate to bring about sRNAbased regulation are being found.
Post-transcriptional Regulation by Small Noncoding RNAs in BacteriaThe idea that RNAs could function as regulators of gene expression has been around since the earliest studies of gene regulation. In their seminal paper entitled "Genetic Regulatory Mechanisms in the Synthesis of Proteins", Jacob and Monod originally hypothesized, "The specific 'repressor' (RNA?), acting with a given operator, is synthesized by a regulator gene" (1). Although the repressor in the case of the lac operon turned out to be the Lac repressor protein, the later discovery of small RNA (sRNA) 3 regulators confirmed their original hypothesis. Currently, examples of this form of gene regulation are widespread among organisms. Here, we will focus on pairing sRNAs in bacteria and, specifically, those that are often termed transencoding sRNAs. These RNAs are expressed from the DNA in trans, i.e. the sRNA genes are far from the genes encoding their mRNA target(s) and have limited complementarity with their target mRNAs. These bacterial sRNAs typically range in length from ϳ50 to 300 nucleotides. Many of these sRNAs are highly expressed when cells are undergoing some type of stress (for instance, oxidative stress, sugar phosphate accumulation, or nutrient starvation). The sRNAs base pair with their mRNA targets, leading to a variety of outcomes. Base pairing can lead to stabilization and/or translational activation of an mRNA target. Usually, activation occurs by base pairing within the 5Ј-UTR, changing folding of the 5Ј-UTR to allow entry of the ribosome and translation to occur (reviewed in Refs. 2 and 3). Another mode of action by sRNAs ultimately leads to translational repression and/or degradation of an mRNA target. In the majority of characterized cases, an sRNA base pairs at or around the ribosome-binding site (RBS) of an mRNA target. This leads to inhibition of translational initiation and, in most cases, the subsequent destabilization of the target. Negative regulation can also occur in other ways, as discussed below. Degradation of the mRNA target reinforces the translational repression and makes it irreversible.In many bacteria, an RNA chaperone, Hfq, is required for efficient base pairing between an sRNA and its target mRNA (reviewed in Ref. 4). In this minireview, we will focus on recent advances in understanding sRNA-mediated negative gene regulation in Escherichia coli and Salmonella enterica. More specifically, ...