Analysis of the CodY RNome reveals RsaD as a stress‐responsive riboregulator of overflow metabolism in <i>Staphylococcus aureus</i>

Augagneur, Yoann; King, Alyssa N.; Germain-Amiot, Noëlla; Sassi, Mohamed; Fitzgerald, John W.; Sahukhal, Gyan S.; Elasri, Mohamed O.; Felden, Brice; Brinsmade, Shaun R.

doi:10.1111/mmi.14418

Cited by 20 publications

(29 citation statements)

References 102 publications

(155 reference statements)

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“…Then, in these conditions, RsaD must be repressed for survival. This work revealed the trans-acting regulatory activity of RsaD on at least one mRNA and highlights the balancing role of this sRNA in carbon overflow and its implications in cell survival (Augagneur et al, 2020). All these mechanisms by which RsaD might be regulated, integrate, and respond to different environmental cues remain to be unveiled.…”

Section: The Blurred Line Between Metabolism and Virulence: Rsad Rsae Rsai And Rsagmentioning

confidence: 88%

“…Nonetheless, the exact mechanism of rsaD regulation by this factor remains uncertain. More recently, Augagneur et al (2020) observed that expression of rsaD is repressed by CodY, a global regulator activated by branched amino-acids and GTP and regulating genes involved in primary metabolism and virulence ( Brinsmade, 2017 ). The promoter region of rsaD contains a putative CodY binding motif, which was detected in at least 15 staphylococcal species, indicating that the regulation of rsaD by CodY is probably conserved ( Augagneur et al, 2020 ).…”

Section: The Blurred Line Between Metabolism and Virulence: Rsad Rsae Rsai And Rsagmentioning

confidence: 99%

“…More recently, Augagneur et al (2020) observed that expression of rsaD is repressed by CodY, a global regulator activated by branched amino-acids and GTP and regulating genes involved in primary metabolism and virulence ( Brinsmade, 2017 ). The promoter region of rsaD contains a putative CodY binding motif, which was detected in at least 15 staphylococcal species, indicating that the regulation of rsaD by CodY is probably conserved ( Augagneur et al, 2020 ). In addition, RsaD is activated during nitric oxide (NO) stress, sensed by the TCS SrrAB ( Bronesky et al, 2019 ) and possibly by the quorum sensing system Agr ( Marroquin et al, 2019 ).…”

Section: The Blurred Line Between Metabolism and Virulence: Rsad Rsae Rsai And Rsagmentioning

confidence: 99%

“…To determine the physiological functions of RsaD, in silico analyses using RNA Predator, TargetRNA2 and IntaRNA identified alsS , which is positively regulated by CodY and whose product is involved in carbon metabolism, as a possible target. RsaD binds the RBS of alsSD mRNA through its C-rich region and inhibits its translation initiation, leading to a decrease in AlsS enzymatic activity ( Augagneur et al, 2020 ). Thus, by repressing RsaD, CodY permits AlsS synthesis.…”

Section: The Blurred Line Between Metabolism and Virulence: Rsad Rsae Rsai And Rsagmentioning

confidence: 99%

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Assembling the Current Pieces: The Puzzle of RNA-Mediated Regulation in Staphylococcus aureus

et al. 2021

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The success of the major opportunistic human Staphylococcus aureus relies on the production of numerous virulence factors, which allow rapid colonization and dissemination in any tissues. Indeed, regulation of its virulence is multifactorial, and based on the production of transcriptional factors, two-component systems (TCS) and small regulatory RNAs (sRNAs). Advances in high-throughput sequencing technologies have unveiled the existence of hundreds of potential RNAs with regulatory functions, but only a fraction of which have been validated in vivo. These discoveries have modified our thinking and understanding of bacterial physiology and virulence fitness by placing sRNAs, alongside transcriptional regulators, at the center of complex and intertwined regulatory networks that allow S. aureus to rapidly adapt to the environmental cues present at infection sites. In this review, we describe the recently acquired knowledge of characterized regulatory RNAs in S. aureus that are associated with metal starvation, nutrient availability, stress responses and virulence. These findings highlight the importance of sRNAs for the comprehension of S. aureus infection processes while raising questions about the interplay between these key regulators and the pathways they control.

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Section: The Blurred Line Between Metabolism and Virulence: Rsad Rsae Rsai And Rsagmentioning

confidence: 88%

Section: The Blurred Line Between Metabolism and Virulence: Rsad Rsae Rsai And Rsagmentioning

confidence: 99%

Section: The Blurred Line Between Metabolism and Virulence: Rsad Rsae Rsai And Rsagmentioning

confidence: 99%

Section: The Blurred Line Between Metabolism and Virulence: Rsad Rsae Rsai And Rsagmentioning

confidence: 99%

See 2 more Smart Citations

Assembling the Current Pieces: The Puzzle of RNA-Mediated Regulation in Staphylococcus aureus

et al. 2021

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“…It might be part of the RsaI regulon, and is induced upon nitric oxide challenge ( Bronesky et al, 2019 ). A study of the CodY regulon identified RsaD as a direct molecular target, and computational tools enabled the authors to find various RsaD mRNA targets including alsS , which encodes α-acetolactate synthase ( Augagneur et al, 2020 ). Through post-transcriptional repression of alsS , RsaD redirects carbon overflow metabolism and regulates cell death during exposure to a weak acid stress.…”

Section: Srna Regulation Is Required For a Variety Of Biological Functionsmentioning

confidence: 99%

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

Felden

Augagneur

2021

Front. Microbiol.

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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.

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Riboregulation in bacteria: From general principles to novel mechanisms of the trp attenuator and its sRNA and peptide products

Evguenieva‐Hackenberg

2021

WIREs RNA

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Gene expression strategies ensuring bacterial survival and competitiveness rely on cis‐ and trans‐acting RNA‐regulators (riboregulators). Among the cis‐acting riboregulators are transcriptional and translational attenuators, and antisense RNAs (asRNAs). The trans‐acting riboregulators are small RNAs (sRNAs) that bind proteins or base pairs with other RNAs. This classification is artificial since some regulatory RNAs act both in cis and in trans, or function in addition as small mRNAs. A prominent example is the archetypical, ribosome‐dependent attenuator of tryptophan (Trp) biosynthesis genes. It responds by transcription attenuation to two signals, Trp availability and inhibition of translation, and gives rise to two trans‐acting products, the attenuator sRNA rnTrpL and the leader peptide peTrpL. In Escherichia coli, rnTrpL links Trp availability to initiation of chromosome replication and in Sinorhizobium meliloti, it coordinates regulation of split tryptophan biosynthesis operons. Furthermore, in S. meliloti, peTrpL is involved in mRNA destabilization in response to antibiotic exposure. It forms two types of asRNA‐containing, antibiotic‐dependent ribonucleoprotein complexes (ARNPs), one of them changing the target specificity of rnTrpL. The posttranscriptional role of peTrpL indicates two emerging paradigms: (1) sRNA reprograming by small molecules and (2) direct involvement of antibiotics in regulatory RNPs. They broaden our view on RNA‐based mechanisms and may inspire new approaches for studying, detecting, and using antibacterial compounds. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Small Molecule‐RNA Interactions RNA Interactions with Proteins and Other Molecules > RNA‐Protein Complexes Regulatory RNAs/RNAi/Riboswitches > Regulatory RNAs

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Analysis of the CodY RNome reveals RsaD as a stress‐responsive riboregulator of overflow metabolism in Staphylococcus aureus

Cited by 20 publications

References 102 publications

Assembling the Current Pieces: The Puzzle of RNA-Mediated Regulation in Staphylococcus aureus

Assembling the Current Pieces: The Puzzle of RNA-Mediated Regulation in Staphylococcus aureus

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

Riboregulation in bacteria: From general principles to novel mechanisms of the trp attenuator and its sRNA and peptide products

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