Impact of bacterial sRNAs in stress responses

Abstract

Bacterial life is harsh and involves numerous environmental and internal challenges that are perceived as stresses. Consequently, adequate responses to survive, cope with, and counteract stress conditions have evolved. In the last few decades, a class of small, non-coding RNAs (sRNAs) has been shown to be involved as key players in stress responses. This review will discuss - primarily from an enterobacterial perspective - selected stress response pathways that involve antisense-type sRNAs. These include themes of how bacteria deal with severe envelope stress, threats of DNA damage, problems with poisoning due to toxic sugar intermediates, issues of iron homeostasis, and nutrient limitation/starvation. The examples discussed highlight how stress relief can be achieved, and how sRNAs act mechanistically in regulatory circuits. For some cases, we will propose scenarios that may suggest why contributions from post-transcriptional control by sRNAs, rather than transcriptional control alone, appear to be a beneficial and universally selected feature.

Keywords: antisense mechanism; bacterial stress response; envelope stress; post-transcriptional regulation; sRNA; starvation.

Figure 1.. sRNA regulators in the envelope stress response.

(A) The outer membrane stress response is triggered by the presence of misfolded OMPs in the periplasm. Release of σ^E up-regulates OMP maintenance genes. However, σ^E cannot directly repress gene expression, but induces three sRNAs (RybB, MicA, and MicL) to silence de novo synthesis of OMPs. Arrows: activation, Lines with bars: repression. (B) Inner membrane stress is sensed by the CpxAR two-component system. Phosphorylated CpxR activates expression of the dual-output cpxP mRNA. CpxP directs misfolded inner membrane proteins (IMPs) for degradation. The sRNA CpxQ, generated from the 3′ segment of cpxP mRNA, targets mRNAs encoding IMPs to shut down their synthesis.

Figure 2.. Phosphosugar stress is relieved through a dual-function sRNA.

During its import, glucose is phosphorylated by the PTS. Excess build-up of intracellular phosphosugars triggers activation of TF SgrR, which induces the sRNA SgrS which is an antisense RNA and encodes a small protein, SgrT. To relieve phosphosugar stress, the antisense function of SgrS silences mRNAs for glucose transporters and activates a phosphatase that dephosphorylates sugars for transport out of the cell. SgrT targets and inactivates glucose transporters.

Figure 3.. sRNAs counteract the effect of inadvertent transcription to stabilize states.

This figure schematically shows effects on the single-cell level (see chapters on biofilm and persistence above). Intrinsic noisiness of transcription leads to inadvertent transcription events at repressed promoters. Without sRNA regulation, inadvertently expressed mRNA will be translated into many proteins and affect the phenotype of the cell. The presence of sRNAs ensures that escaping mRNAs are ‘caught’ at the post-transcriptional level, enforcing the repressed state.