Regulation by small RNAs in bacteria: expanding frontiers

Abstract

Research on the discovery and characterization of small, regulatory RNAs in bacteria has exploded in recent years. These sRNAs act by base pairing with target mRNAs with which they share limited or extended complementarity, or by modulating protein activity, in some cases by mimicking other nucleic acids. Mechanistic insights into how sRNAs bind mRNAs and proteins, how they compete with each other, and how they interface with ribonucleases are active areas of discovery. Current work also has begun to illuminate how sRNAs modulate expression of distinct regulons and key transcription factors, thus integrating sRNA activity into extensive regulatory networks. In addition, the application of RNA deep sequencing has led to reports of hundreds of additional sRNA candidates in a wide swath of bacterial species. Most importantly, recent studies have served to clarify the abundance of remaining questions about how, when, and why sRNA-mediated regulation is of such importance to bacterial lifestyles.

Figure 1. General Properties of Trans-encoded Base Pairing sRNAs

(A) Diagram showing the modular structure of Hfq-binding sRNAs. The most highly conserved regions in seven enteric sRNAs are shaded gray. This conservation generally corresponds to the region(s) of the sRNA involved in base pairing, frequently occurring at the 5’ end, but corresponding to two and three regions of base pairing for FnrS and Spot42, respectively. (B) Diagram showing the different positions at which sRNAs can block ribosome binding. (C) Diagram showing ways by which base paired sRNAs can direct RNase E-mediated target mRNA processing.

Figure 2. General Properties of sRNAs That Modulate Protein Activity

Bacterial sRNA binding to proteins has been demonstrated to inhibit and/or modify protein activities. It is proposed that sRNA binding to proteins also can activate or to bring two or more proteins into together. The association of sRNA and proteins is likely to be influenced by many different factors, and the disassociation can be actively or passively controlled.

Figure 3. Networks Regulated by Trans-encoded Base Pairing sRNAs in E. coli

The network is based on a compilation of published interactions. Boxes represent sRNAs and ovals represent mRNA targets. Ovals corresponding to mRNAs encoding transcription regulators are colored blue. Red lines indicate negative regulation, green lines indicate positive regulation and gray lines indicate base pairing but no effect on the target. The thickness of the lines indicates the level of proof for base pairing; compensatory mutation analysis supports those interactions represented with the thickest lines. A limited number of lines emanating from an sRNA may reflect incomplete characterization or the fact that the sRNA has only few targets.