Molecular call and response: the physiology of bacterial small RNAs

Abstract

The vital role of bacterial small RNAs (sRNAs) in cellular regulation is now well-established. Although many diverse mechanisms by which sRNAs bring about changes in gene expression have been thoroughly described, comparatively less is known about their biological roles and effects on cell physiology. Nevertheless, for some sRNAs, insight has been gained into the intricate regulatory interplay that is required to sense external environmental and internal metabolic cues and turn them into physiological outcomes. Here, we review examples of regulation by selected sRNAs, emphasizing signals and regulators required for sRNA expression, sRNA regulatory targets, and the resulting consequences for the cell. We highlight sRNAs involved in regulation of the processes of iron homeostasis (RyhB, PrrF, and FsrA) and carbon metabolism (Spot 42, CyaR, and SgrS).

Figure 1

Selected mechanisms of regulation by trans-encoded sRNAs. Small RNAs (sRNAs) are designated by gray lines, and their messenger RNA (mRNA) targets are denoted by black arrows. White boxes represent ribosome binding sites (RBSs) of mRNAs. Series of small, thin lines signify complementary base pairing between an sRNA and its target mRNA. mRNA degradation by RNase E degradosome (black, wedged circles) is represented by broken black arrows. Gray arrow denotes transition before and after sRNA base pairing. See Section 1 for details.

Figure 2

Regulation and physiology of the response to glucose-phosphate stress. The PTS phosphorelay cascade (orange) leads to activation/phosphorylation (yellow circles) of both the PtsG (dark blue) and ManXYZ (light blue) sugar transporters. Glucose-phosphate stress occurs when glucose or its analogs αMG (red hexagons) and 2DG (purple hexagons) are phosphorylated upon entry through the transporters and accumulate in the cell, inhibiting growth. An unknown signal (gold sun shape) activates the transcriptional regulator SgrR (gray), which in turn activates transcription of the regulatory sRNA SgrS (green line). Associated with the sRNA chaperone Hfq (light blue hexamer), SgrS base pairs with both ptsG and manXYZ mRNAs (blue lines), blocking translation and resulting in subsequent degradation by the RNase E degradosome (black, wedged circles). In addition, SgrS encodes a small peptide, SgrT (green cylinder), which inhibits the sugar transport activity of PtsG through an undefined mechanism. See text for details.