Small RNAs, Large Networks: Posttranscriptional Regulons in Gram-Negative Bacteria

Abstract

Small regulatory RNA (sRNAs) are key mediators of posttranscriptional gene control in bacteria. Assisted by RNA-binding proteins, a single sRNA often modulates the expression of dozens of genes, and thus sRNAs frequently adopt central roles in regulatory networks. Posttranscriptional regulation by sRNAs comes with several unique features that cannot be achieved by transcriptional regulators. However, for optimal network performance, transcriptional and posttranscriptional control mechanisms typically go hand-in-hand. This view is reflected by the ever-growing class of mixed network motifs involving sRNAs and transcription factors, which are ubiquitous in biology and whose regulatory properties we are beginning to understand. In addition, sRNA activity can be antagonized by base-pairing with sponge RNAs, adding yet another layer of complexity to these networks. In this article, we summarize the regulatory concepts underlying sRNA-mediated gene control in bacteria and discuss how sRNAs shape the output of a network, focusing on several key examples. Expected final online publication date for the Annual Review of Microbiology, Volume 77 is September 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Interplay of two small RNAs fine-tunes hierarchical flagellar gene expression in the foodborne pathogenCampylobacter jejuni

“…S. aureus RNases J1/J2, for example, trim the 5' end of uhpT mRNA to generate the 3'UTR-derived sRNA RsaG (Desgranges et al, 2022), and Bacillus subtilis RNase J1 trims the signal recognition particle (SRP) RNA component scRNA (small cytoplasmic RNA) after processing by RNase III (Yao et al, 2007). While 3'UTR-derived sRNAs control multiple physiological processes in diverse bacterial species (Miyakoshi et al, 2015;Ponath et al, 2022), also with implications for larger regulatory networks such as the bacterial envelope stress response (Chao and Vogel, 2016;Papenfort and Melamed, 2023), processing of flagellar mRNAs to produce sRNAs that function in the same pathway is a relatively new concept. To the best of our knowledge, only two sRNAs that potentially repress flagellar biogenesis and are also processed from flagellar mRNAs have been reported in E. coli: FlgO and FliX, which are processed from the 3'UTRs of FliA-dependent flgL and fliC mRNAs, respectively (Melamed et al, 2021;Thomason et al, 2015).…”

In vivo RNA interactome profiling reveals 3’UTR-processed small RNA targeting a central regulatory hub

“…Vice versa, functionally important mRNAs (such as the general stress regulator rpoS and bio lm regulator csgD) are targeted by several different sRNAs, which have been conceptualized as mRNA regulatory hubs (Boehm and Vogel, 2012). These mRNAs and regulatory sRNAs thus constitute a large and intricate RNA-RNA interaction network involving hundreds of genes in bacteria (Papenfort and Melamed, 2023;Svensson and Chao, 2022). The scale of this RNA-RNA network now begins to rival that of the protein-protein and protein-DNA interaction networks, and covers all aspects of bacterial physiology including central metabolism, cell shape, envelope integrity, quorum sensing, bio lm formation, antibiotic resistance, host infection, symbiosis and more (Cao et al, 2023;De Mets et al, 2019;Huber et al, 2022Huber et al, , 2020Miyakoshi et al, 2019;Neubacher et al, 2020;Peschek et al, 2020;Westermann et al, 2016).…”

Small RNA regulation of an essential process induces bacterial resistance to aminoglycosides during oxidative stress

“…Bacteria, in particular, have developed a remarkable ability to modify their physiology through genetic regulations, enabling them to quickly return to a state of balance. In recent years, small regulatory RNAs (sRNAs) have emerged as key actors in such adaptative responses in bacteria (1–4). sRNAs are post-transcriptional regulators that bind to multiple target mRNAs, modifying their translation and/or stability (5, 6).…”