The Mechanisms of Virulence Regulation by Small Noncoding RNAs in Low GC Gram-Positive Pathogens

Pitman, Stephanie; Cho, Kyu Hong

doi:10.3390/ijms161226194

Cited by 17 publications

(14 citation statements)

References 92 publications

(189 reference statements)

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“…Surprisingly, inactivation of Hfq, an sRNA chaperone well described in Gram-negative bacteria, did not yield any alterations in the levels of transcripts of three analyzed sRNAs (i.e., teg49, teg23, and teg35). This finding indicated that Hfq does not have a major role in stabilizing sRNA in S. aureus, consistent with other reports of Gram-positive bacteria (23).…”

Section: Figsupporting

confidence: 92%

“…The discovery of sRNAs in bacteria in the last 2 decades has provided new insights into gene regulation. sRNAs have been found to be ubiquitous and represent the most abundant class of posttranscriptional regulators in prokaryotes (21)(22)(23). Most of the sRNAs act by base pairing with target mRNAs.…”

Section: Discussionmentioning

confidence: 99%

“…Most of the sRNAs act by base pairing with target mRNAs. However, the majority of sRNA studies have been limited to Escherichia coli and other Gram-negative bacteria (23). With the…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it was shown that a number of small RNAs (sRNAs) are involved in the regulation of virulence genes in various organisms, including S. aureus (21)(22)(23)(24). Small RNAs are classified based on their target regulation: cis-acting sRNAs, such as in binding to the complementary mRNA (antisense), or trans-acting, such as those that bind target RNA or proteins at distal sites (21).…”

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confidence: 99%

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Small RNA teg49 Is Derived from a sarA Transcript and Regulates Virulence Genes Independent of SarA in Staphylococcus aureus

et al. 2018

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Expression of virulence factors in is regulated by a wide range of transcriptional regulators, including proteins and small RNAs (sRNAs), at the level of transcription and/or translation. The locus consists of three overlapping transcripts generated from three distinct promoters, all containing the open reading frame (ORF). The 5' untranslated regions (UTRs) of these transcripts contain three separate regions ∼711, 409, and 146 nucleotides (nt) upstream of the translation start, the functions of which remain unknown. Recent transcriptome-sequencing (RNA-Seq) analysis and subsequent characterization indicated that two sRNAs, teg49 and teg48, are processed and likely produced from the P3 and P1 transcripts of the locus, respectively. In this report, we utilized a variety of promoter mutants and and mutants to ascertain the contributions of these factors to the generation of teg49. We also defined the transcriptional regulon of teg49, including virulence genes not regulated by SarA. Phenotypically, teg49 did not impact biofilm formation or affect overall SarA expression significantly. Comparative analyses of RNA-Seq data between the wild-type, teg49 mutant, and mutant strains indicated that ∼133 genes are significantly upregulated while 97 are downregulated in a teg49 deletion mutant in a-independent manner. An abscess model of skin infection indicated that the teg49 mutant exhibited a reduced bacterial load compared to the wild-type Overall, these results suggest that teg49 sRNA has a regulatory role in target gene regulation independent of SarA. The exact mechanism of this regulation is yet to be dissected.

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Section: Figsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

“…Most of the sRNAs act by base pairing with target mRNAs. However, the majority of sRNA studies have been limited to Escherichia coli and other Gram-negative bacteria (23). With the…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Small RNA teg49 Is Derived from a sarA Transcript and Regulates Virulence Genes Independent of SarA in Staphylococcus aureus

et al. 2018

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“…Premature transcription termination (PTT) within 5' untranslated regions were recently shown to be widespread events in the Gram-positive bacteria B. subtilis, Listeria monocytogenes and Enterococcus faecalis (Dar et al, 2016 (Bohn et al, 2010;Rochat et al, 2018) and also to promote biofilm formation in Staphylococcus epidermidis by supporting extracellular DNA release and the production of polysaccharideintercellular adhesin (PIA) (Schoenfelder et al, 2019). However, the function of Hfq in facilitating the interactions between sRNA regulators and their target mRNAs in Gram-positive bacteria remains elusive, since most of the known sRNAs seem to exert their regulatory activity independent of this global RNA-binding protein (Pitman and Cho, 2015).…”

Section: Discovery Of Novel Regulatory Functions Located In 5' Utrsmentioning

confidence: 99%

An RNA-centric global view ofClostridioides difficilereveals broad activity of Hfq in a clinically important Gram-positive bacterium

Fuchs

Lamm‐Schmidt

Ponath

et al. 2020

Preprint

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The Gram-positive human pathogen Clostridioides difficile has emerged as the leading cause of antibiotic-associated diarrhea. Despite growing evidence for a role of Hfq in RNA-based gene regulation in C. difficile, little is known about the bacterium′s transcriptome architecture and mechanisms of post-transcriptional control. Here, we have applied a suite of RNA-centric techniques, including transcription start site mapping, transcription termination mapping and Hfq RIP-seq, to generate a single-nucleotide resolution RNA map of C. difficile 630. Our transcriptome annotation provides information about 5′ and 3′ untranslated regions, operon structures and non-coding regulators, including 42 sRNAs. These transcriptome data are accessible via an open-access browser called ′Clost-Base′. Our results indicate functionality of many conserved riboswitches and predict novel cis-regulatory elements upstream of MDR-type ABC transporters and transcriptional regulators. Recent studies have revealed a role of sRNA-based regulation in several Gram-positive bacteria but their involvement with the RNA-binding protein Hfq remains controversial. Here, sequencing the RNA ligands of Hfq reveals in vivo association of many sRNAs along with hundreds of potential target mRNAs in C. difficile providing evidence for a global role of Hfq in post-transcriptional regulation in a Gram-positive bacterium. Through integration of Hfq-bound transcripts and computational approaches we predict regulated target mRNAs for the novel sRNA AtcS encoding several adhesins and the conserved oligopeptide transporter oppB that influences sporulation initiation in C. difficile. Overall, these findings provide a potential mechanistic explanation for increased biofilm formation and sporulation in an hfq deletion strain and lay the foundation for understanding clostridial ribo-regulation with implications for the infection process.

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Small Regulatory RNAs in Bacteria

Delihas

2016

Encyclopedia of Life Sciences

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Intergenic regions of bacteria contain small regulatory ribonucleic acid (sRNA) genes whose transcripts control expression of distal genes. These transcripts, referred to as sRNAs, primarily act at the level of translation where they bind messenger ribonucleic acids (mRNAs) and inhibit or activate a target mRNA. Base pairing with mRNAs is generally imperfect and can include noncanonical base pairs. The RNA chaperone protein Hfq is involved in many RNA/RNA interactions and ribonucleases RNase E and RNase III have been implicated in destabilisation of target mRNAs. Many sRNAs can inhibit multiple mRNAs; however, some sRNAs bind proteins and can regulate transcription or translation indirectly. Some act like ‘sponges’ that bind and sequester proteins involved in global gene regulation. Many sRNA genes are activated by environmental stress factors, and the sRNA genes have complex upstream regulatory sites. Further insight into broad functions of sRNAs comes from human host cells infected by pathogenic bacteria, which reveals a role of sRNA in both virulence and response in human host cell molecular functions, for example changes in long noncoding RNAs and microRNAs. Bacterial regulatory RNAs are proving to be remarkable factors in both cell physiology and bacterial pathogenesis and these RNAs have opened a new world in molecular biology. Key Concepts Small regulatory RNA genes have been found in most bacterial species. sRNA transcripts are generally less than 200 nt. sRNAs can control gene expression at the level of translation or transcription. sRNAs respond to environmental or internal stress conditions. sRNAs generally form small and imperfect RNA/RNA base pairing with target mRNA; noncanonical base pairs can also be present. sRNAs can inhibit translational and/or induce degradation of target mRNA. Many sRNAs regulate multiple target mRNAs. sRNAs can indirectly regulate the expression of global genes, some by binding proteins that control gene expression. sRNAs can play a major role in bacterial pathogenicity and influence eukaryotic host molecular functions such as levels of host cell microRNA and long noncoding RNA.

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The Mechanisms of Virulence Regulation by Small Noncoding RNAs in Low GC Gram-Positive Pathogens

Cited by 17 publications

References 92 publications

Small RNA teg49 Is Derived from a sarA Transcript and Regulates Virulence Genes Independent of SarA in Staphylococcus aureus

Small RNA teg49 Is Derived from a sarA Transcript and Regulates Virulence Genes Independent of SarA in Staphylococcus aureus

An RNA-centric global view ofClostridioides difficilereveals broad activity of Hfq in a clinically important Gram-positive bacterium

Small Regulatory RNAs in Bacteria

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