Diversity and Versatility in Small RNA-Mediated Regulation in Bacterial Pathogens

Abstract

Bacterial gene expression is under the control of a large set of molecules acting at multiple levels. In addition to the transcription factors (TFs) already known to be involved in global regulation of gene expression, small regulatory RNAs (sRNAs) are emerging as major players in gene regulatory networks, where they allow environmental adaptation and fitness. Developments in high-throughput screening have enabled their detection in the entire bacterial kingdom. These sRNAs influence a plethora of biological processes, including but not limited to outer membrane synthesis, metabolism, TF regulation, transcription termination, virulence, and antibiotic resistance and persistence. Almost always noncoding, they regulate target genes at the post-transcriptional level, usually through base-pair interactions with mRNAs, alone or with the help of dedicated chaperones. There is growing evidence that sRNA-mediated mechanisms of actions are far more diverse than initially thought, and that they go beyond the so-called cis- and trans-encoded classifications. These molecules can be derived and processed from 5' untranslated regions (UTRs), coding or non-coding sequences, and even from 3' UTRs. They usually act within the bacterial cytoplasm, but recent studies showed sRNAs in extracellular vesicles, where they influence host cell interactions. In this review, we highlight the various functions of sRNAs in bacterial pathogens, and focus on the increasing examples of widely diverse regulatory mechanisms that might compel us to reconsider what constitute the sRNA.

Development of ONT-cappable-seq to unravel the transcriptional landscape of Pseudomonas phages

“…By contrast, the shortest sRNA candidate, sRNA3, seemingly lacks an annotated TSS, suggesting that this fragment is derived from a primary precursor through processing events. Functional sRNA biogenesis through RNase activity has already been demonstrated in various bacteria [68] , [69] , [70] , and was recently also suggested to occur in Pseudomonas phage phiKZ [71] . In addition, the biological relevance of small non-coding RNAs in the regulation of phage and host development is increasingly being recognized in several other Pseudomonas phages [5] , [72] .…”

Development of ONT-cappable-seq to unravel the transcriptional landscape of Pseudomonas phages

“…Functional sRNA biogenesis through RNase activity has already been demonstrated in various bacteria (64)(65)(66), and was recently also suggested to occur in Pseudomonas phage phiKZ (67). In addition, the biological relevance of small non-coding RNAs in the regulation of phage and host development is increasingly being recognized in several other Pseudomonas phages (5,68).…”

Thirty Years of sRNA-Mediated Regulation in Staphylococcus aureus: From Initial Discoveries to In Vivo Biological Implications

“…However, recent discoveries have shown exquisite modes of biogenesis with the identification of 5 and 3 UTR-derived sRNAs, which indicates that sRNAs that do not perfectly fit the usual features may no longer be considered exceptions [4]. Therefore, although they are often referred to as sRNAs (for small RNAs), a more appropriate term would be regulatory RNAs, given that they interact with many actors to perform their regulatory functions [5,6]. For simplicity, we will keep referring to them as sRNAs hereafter.…”

“…For simplicity, we will keep referring to them as sRNAs hereafter. To regulate their targets, they act as repressors or activators through the modification of ribosome accessibility and/or mRNA stability [2,6]. The binding of sRNA repressors results in translation inhibition by preventing ribosome loading, or else recruits an RNase for mRNA degradation.…”