Impacts of Small RNAs and Their Chaperones on Bacterial Pathogenicity

Abstract

Bacterial small RNAs (sRNAs) are critical post-transcriptional regulators that exert broad effects on cell physiology. One class of sRNAs, referred to as trans-acting sRNAs, base-pairs with mRNAs to cause changes in their stability or translation. Another class of sRNAs sequesters RNA-binding proteins that in turn modulate mRNA expression. RNA chaperones play key roles in these regulatory events by promoting base-pairing of sRNAs to mRNAs, increasing the stability of sRNAs, inducing conformational changes on mRNA targets upon binding, or by titrating sRNAs away from their primary targets. In pathogenic bacteria, sRNAs and their chaperones exert broad impacts on both cell physiology and virulence, highlighting the central role of these systems in pathogenesis. This review provides an overview of the growing number and roles of these chaperone proteins in sRNA regulation, highlighting how these proteins contribute to bacterial pathogenesis.

Bacterial RNA chaperones and chaperone-like riboregulators: behind the scenes of RNA-mediated regulation of cellular metabolism

“…Hfq has been shown to influence numerous complex bacterial phenotypes, such as growth rates and yields, cell size, osmosensitivity, oxidation of carbon sources and sensitivity to ultraviolet light [ 8 ], stress response and virulence [ 9 ]. At present, Hfq is perceived as one of the main players in post-transcriptional regulation of gene expression in Enterobacteriaceae, where it aids regulation of transcripts through direct interaction, as well as by stabilising small, non-coding RNAs (sRNAs) and matching them with their RNA targets [ 7 , 10 ].…”

“…sRNAs have different modes of binding to Hfq and are generally classified into two groups – Class I or Class II – based on their proposed modes of interaction [ 10 , 30 ]. Class I sRNAs interact with the proximal face of Hfq, through U-rich stretches at the 3’ end, and with the rim of the chaperone, via U/A-rich regions [ 23 , 24 ].…”

“…Their targets (named accordingly Class I mRNAs) have (ARN)n motifs through which they can bind to the distal face of Hfq [ 31 ]. In contrast, Class II sRNAs bind to the proximal and distal faces of Hfq through U-rich and (ARN)n motifs, respectively, and their targets Class II mRNAs interact with the rim through U/A rich motifs [ 10 , 32 ].…”

“…Different studies have focused on the competition between RNA molecules for the binding to Hfq showing that certain RNAs can outcompete others [ 32 , 45 , 48 ]. For instance, it is generally accepted that Class II sRNAs have stronger interactions with Hfq and can outcompete Class I sRNAs [ 10 , 32 ]. Through their double interaction with the proximal and distal faces of Hfq, Class II sRNAs can also displace Class I mRNAs, predicted to interact with the distal face of Hfq [ 34 ].…”

The RNA Chaperone Protein Hfq Regulates the Characteristic Sporulation and Insecticidal Activity of Bacillus thuringiensis

“…The proximal face is the side with an exposed N-terminal (α-helix that preferentially binds small RNAs (sRNAs) carrying U-rich internal motifs and a U-tailed terminator, whereas the distal face is located on the other side of the proximal face and preferentially binds target mRNAs with A-rich motifs that are often present in the 5′-untranslated regions and ribosome-binding sites. With these two polar faces and rim face, Hfq is found to regulate various physiological activities of bacteria by binding to different kinds of RNAs (mainly sRNAs and mRNAs) and affects their stability or translation processes ( Updegrove et al, 2010 ; Vogel and Luisi, 2011 ; De Lay et al, 2013 ; Djapgne and Oglesby, 2021 ). For example, Hfq is able to interact directly with some sRNAs ( Møller et al, 2002 ), such as RyhB to increase its stability in regulating iron metabolism in E. coli ( Massé et al, 2003 ), or RsmY to control the quorum sensing of Pseudomonas aeruginosa ( Sonnleitner et al, 2006 ).…”