Current knowledge on regulatory RNAs and their machineries in<i>Staphylococcus aureus</i>

Romilly, Cédric; Caldelari, Isabelle; Parmentier, Delphine; Lioliou, Efthimia; Romby, Pascale; Fechter, Pierre

doi:10.4161/rna.20103

Cited by 46 publications

(38 citation statements)

References 121 publications

(232 reference statements)

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“…Several examples of regulation by direct interaction between RNAIII and its target mRNAs have been reported (10)(11)(12)(13)(14). A common denominator in these regulatory interactions is the targeting of translation initiation sequences, through base pairing of the CU-rich loop domains of RNAIII with regions containing the Shine and Dalgarno (SD) sequence or AUG start codon of the target mRNA, resulting in negative control of translation (15,16). A notable exception is the activation of Hla by RNAIII, in which the interaction unmasks the SD sequence to facilitate translation of hla mRNA (10).…”

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confidence: 99%

RNAIII of the Staphylococcus aureus agr system activates global regulator MgrA by stabilizing mRNA

Gupta

Luong

Lee

2015

Proc. Natl. Acad. Sci. U.S.A.

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RNAIII, the effector of the agr quorum-sensing system, plays a key role in virulence gene regulation in Staphylococcus aureus, but how RNAIII transcriptionally regulates its downstream genes is not completely understood. Here, we show that RNAIII stabilizes mgrA mRNA, thereby increasing the production of MgrA, a global transcriptional regulator that affects the expression of many genes. The mgrA gene is transcribed from two promoters, P1 and P2, to produce two mRNA transcripts with long 5′ UTR. Two adjacent regions of the mgrA mRNA UTR transcribed from the upstream P2 promoter, but not the P1 promoter, form a stable complex with two regions of RNAIII near the 5′ and 3′ ends. We further demonstrate that the interaction has several biological effects. We propose that MgrA can serve as an intermediary regulator through which agr exerts its regulatory function.

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confidence: 99%

RNAIII of the Staphylococcus aureus agr system activates global regulator MgrA by stabilizing mRNA

Gupta

Luong

Lee

2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Hfq is present in most of the staphylococcal genomes, but differentially expressed (Liu et al, 2010). Its role in vivo is still controversial, while an hfq deletion mutant has no significant phenotype (Bohn et al, 2007;Romilly et al, 2012a). Several sRNAs, such as RNAIII or RsaE, and SprD, repress their target mRNAs either by forming long irregular duplexes, or by forming bi-partite binding sites involving distant and unpaired regions of both RNAs.…”

Section: Hfq Protein a Mysterious Protein In S Aureusmentioning

confidence: 99%

“…As a regulator, RNAIII promotes the switch between the expression of surface proteins and the synthesis of excreted toxins in a time-dependent manner (Novick, 2003). The regulation mechanisms by RNAIII have been extensively documented in the last years (reviewed in Caldelari et al, 2011;Romby and Charpentier, 2010;Romilly et al, 2012a). It controls gene expression at the post-transcriptional level via an antisense mechanism.…”

Section: S Aureus Rnaiii Regulates the Temporal Expression Of Virulementioning

confidence: 99%

“…In S. aureus, the first reported regulatory RNA, the so-called RNAIII, was shown to be one of the main intracellular effectors of the agr quorum-sensing system (Novick and Geisinger, 2008;Novick et al, 1993). Later on, research on the discovery and functional characterization of sRNAs in S. aureus has exploded leading to an impressive repertoire of various regulatory RNAs (reviewed in Felden et al, 2011;Romilly et al, 2012a). Approaches for identifications were based on various computing softwares (Geissmann et al, 2009;Marchais et al, 2009;Pichon and Felden, 2005), Affymetrix microarrays Roberts et al, 2006) and tiling arrays (Lasa et al, 2011), conventional cloning/sequencing of small sized cDNAs (Abu-Qatouseh et al, 2010), and high throughput sequencing (Beaume et al, 2010;Bohn et al, 2010;Howden et al, 2013;Lasa et al, 2011;Lioliou et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…This large variety of lifestyles is due to the fact that the bacteria produces a large array of virulence factors responsible for adhesion, invasion, and dissemination in host tissues, the acquisition of nutrients, and for combating the host immune system (Novick, 2003). In addition, two component systems, transcriptional regulatory proteins, and RNAs form intricate interactions and regulatory circuits that sense and respond to a large variety of signals to coordinate gene expression in a dynamic manner (Cheung et al, 2004;Romilly et al, 2012a).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The importance of regulatory RNAs in Staphylococcus aureus

Tomasini

François

Howden

et al. 2014

Infection, Genetics and Evolution

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a b s t r a c t RNA molecules with regulatory functions in pathogenic bacteria have benefited from a renewed interest these two last decades. In Staphylococcus aureus, recent genome-wide approaches have led to the discovery that almost 10-20% of genes code for RNAs with critical regulatory roles in adaptive processes. These RNAs include trans-acting RNAs, which mostly act through binding to target mRNAs, and cis-acting RNAs, which include regulatory regions of mRNAs responding to various metabolic signals. Besides recent analysis of S. aureus transcriptome has revealed an unprecedented existence of pervasive transcription generating a high number of weakly expressed antisense RNAs along the genome as well as numerous mRNAs with overlapped regions. Here, we will illustrate the diversity of trans-acting RNAs and illustrate how they are integrated into complex regulatory circuits, which link metabolism, stress response and virulence.

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Reducing the Bottleneck in Discovery of Novel Antibiotics

et al. 2016

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Most antibiotics were discovered by screening soil actinomycetes, but the efficiency of the discovery platform collapsed in the 1960s. By now, more than 3000 antibiotics have been described and most of the current discovery effort is focused on the rediscovery of known compounds, making the approach impractical. The last marketed broad-spectrum antibiotics discovered were daptomycin, linezolid, and fidaxomicin. The current state of the art in the development of new anti-infectives is a non-existent pipeline in the absence of a discovery platform. This is particularly troubling given the emergence of pan-resistant pathogens. The current practice in dealing with the problem of the background of known compounds is to use chemical dereplication of extracts to assess the relative novelty of a compound it contains. Dereplication typically requires scale-up, extraction, and often fractionation before an accurate mass and structure can be produced by MS analysis in combination with 2D NMR. Here, we describe a transcriptome analysis approach using RNA sequencing (RNASeq) to identify promising novel antimicrobial compounds from microbial extracts. Our pipeline permits identification of antimicrobial compounds that produce distinct transcription profiles using unfractionated cell extracts. This efficient pipeline will eliminate the requirement for purification and structure determination of compounds from extracts and will facilitate high-throughput screen of cell extracts for identification of novel compounds.

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Current knowledge on regulatory RNAs and their machineries inStaphylococcus aureus

Cited by 46 publications

References 121 publications

RNAIII of the Staphylococcus aureus agr system activates global regulator MgrA by stabilizing mRNA

RNAIII of the Staphylococcus aureus agr system activates global regulator MgrA by stabilizing mRNA

The importance of regulatory RNAs in Staphylococcus aureus

Reducing the Bottleneck in Discovery of Novel Antibiotics

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