Iron-responsive bacterial small RNAs: variations on a theme

Abstract

For most living organisms, iron is both essential and potentially toxic, making the precise maintenance of iron homeostasis necessary for survival. To manage this paradox, bacteria regulate the acquisition, utilization, and storage of iron in response to its availability. The iron-dependent ferric uptake repressor (Fur) often mediates this iron-responsive regulation, by both direct and indirect mechanisms. In 2002, Masse and Gottesman identified a novel target of Fur-mediated regulation in Escherichia coli: a gene encoding a small regulatory RNA (sRNA) termed RyhB. Under conditions of iron-limitation, RyhB is produced and functions to regulate the expression of several target genes encoding iron-utilizing enzymes, iron acquisition systems, and iron storage factors. This pivotal finding provided the missing link between environmental iron-limitation and previously observed decreases in certain iron-dependent metabolic pathways, a phenomenon now referred to as an “iron-sparing” response. The discovery of RyhB opened the door to the rapidly expanding field of bacterial iron-regulated sRNAs, which continue to be identified and described in numerous bacterial species. Most striking are findings that the impact of iron-responsive sRNA regulation often extends beyond iron homeostasis, particularly with regard to production of virulence-associated factors by pathogenic bacteria. This review discusses trends in the collective body of work on iron-regulated sRNAs, highlighting both the regulatory mechanisms they utilize to control target gene expression and the impact of this regulation on basic processes controlling bacterial physiology and virulence.

The Small RNA RyhB Contributes to Siderophore Production and Virulence of Uropathogenic Escherichia coli

“…S. enterica encodes two homologs of RyhB, RyhB-1 and RyhB-2 (also termed RfrA and RfrB). They are involved in protection against oxidative stress, bactericidal antibiotic and acid resistance, and survival within epithelial cells and macrophages (7,61). RyhB-2 is also implicated in the regulation of motility in S. Typhimurium, and the highest expression of both sRNAs in S. Typhi was obtained during interaction with host cells, which correlates with their role in virulence (27,62).…”

“…Iron is thus both essential and potentially toxic for most living organisms, making the precise maintenance of iron homeostasis necessary for survival (2)(3)(4). In E. coli, iron acquisition and storage control is mediated by the global ferric uptake regulator (Fur) and the sRNA RyhB (1,(5)(6)(7). Under iron-rich conditions, Fe 2ϩ -Fur acts as a negative regulator of ryhB and iron uptake genes.…”

An Intimate Link: Two-Component Signal Transduction Systems and Metal Transport Systems in Bacteria

“…As a result, the RR can activate or inhibit the transcription of target genes required for an adaptive response. Another group of regulatory proteins include cytoplasmic metalloregulators, which unlike TCSTSs are comprised of a single protein that can perform dual functions of sensing and responding to metal ions [17–19]. In fact, these proteins are specialized allosteric proteins that can directly bind to a specific or a small number of cognate metal ions [17,18,20].…”

“…Upon binding, the protein undergoes a conformational change in the regulatory region allowing it to control the transcription of target genes [18]. The products encoded by these genes can have multiple functions and may include proteins involved in growth, stress tolerance, virulence and metal trafficking within or between cellular compartments [17–19]. The function, mechanism and ion specificity of metalloregulators have been previously reviewed by others [17–18,20].…”

Rapid and high-throughput construction of microbial cell-factories with regulatory noncoding RNAs

“…Similarly, MicC sRNA represses the translation of another outer-membrane protein OmpC by preventing ribosome recruitment which is mediated by 22 nucleotides of MicC that are complementary to the translation initiation region of ompC mRNA (Chen et al, 2004). The 90 nucleotides-long RyhB, encoded by the ryhB, down-regulates a set of iron-storage, iron acquisition systems and iron-using proteins upon iron depletion (Masse and Gottesman, 2002;Oglesby-Sherrouse and Murphy, 2013). Moreover, RyhB promotes siderophore production by directly repressing the translation of serine acetyltransferase (cysE), allowing serine to be used as building blocks for enterobactin synthesis through the nonribosomal peptide synthetase (NRPS) pathway, indicating its comprehensive role in metabolic regulation (Salvail et al, 2010).…”