The ancestral SgrS RNA discriminates horizontally acquired
            <i>Salmonella</i>
            mRNAs through a single G-U wobble pair

Papenfort, Kai; Podkaminski, Dimitri; Hinton, Jay C. D.; Vogel, Jörg

doi:10.1073/pnas.1119414109

Cited by 83 publications

(73 citation statements)

References 66 publications

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“…S3 and S4, sgrS mutant alleles regulated expression of both manXYZ and yigL similarly to wild-type SgrS. These results are consistent with observations by other groups, where mutations in sgrT translation sequences had neutral effects on regulation of SgrS targets in S. Typhimurium, i.e., yigL and sopD (which encodes a secreted virulence factor in S. Typhimurium) (10,15). In sum, these data indicate that mutations that impair sgrT translation or change the distance between sgrT and the base-pairing region have no major effect on the ability of SgrS to regulate mRNA targets via base pairing.…”

supporting

confidence: 81%

Deciphering the Interplay between Two Independent Functions of the Small RNA Regulator SgrS in Salmonella

Balasubramanian

Vanderpool

2013

J Bacteriol

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Bacterial dual-function small RNAs regulate gene expression by RNA-RNA base pairing and also code for small proteins. SgrS is a dual-function small RNA in Escherichia coli and Salmonella that is expressed under stress conditions associated with accumulation of sugar-phosphates, and its activity is crucial for growth during stress. The base-pairing function of SgrS regulates a number of mRNA targets, resulting in reduced uptake and enhanced efflux of sugars. SgrS also encodes the SgrT protein, which reduces sugar uptake by a mechanism that is independent of base pairing. While SgrS base-pairing activity has been characterized in detail, little is known about how base pairing and translation of sgrT are coordinated. In the current study, we utilized a series of mutants to determine how translation of sgrT affected the efficiency of base pairing-dependent regulation and vice versa. Mutations that abrogated sgrT translation had minimal effects on base-pairing activity. Conversely, mutations that impaired base-pairing interactions resulted in increased SgrT production. Furthermore, while ectopic overexpression of sgrS mutant alleles lacking only one of the two functions rescued cell growth under stress conditions, the SgrS base-pairing function alone was indispensable for growth rescue when alleles were expressed from the native locus. Collectively, the results suggest that during stress, repression of sugar transporter synthesis via base pairing with sugar transporter mRNAs is the first priority of SgrS. Subsequently, SgrT is made and acts on preexisting transporters. The combined action of these two functions produces an effective stress response. In the past decade, a vast number of small RNAs (sRNAs) have been identified as important posttranscriptional regulators. In bacteria, sRNAs typically do not encode proteins. Rather, they regulate gene expression by binding to target mRNAs via basepairing interactions, resulting in enhanced (positive regulation) or reduced (negative regulation) translation. With the identification of new sRNAs, it is increasingly clear that some sRNAs, dubbed dual-function sRNAs, not only act as canonical sRNAs by regulating targets via a base-pairing mechanism but also encode regulatory proteins (1). While the noncoding, base-pairing sRNA mechanisms have been studied extensively (reviewed in references 2 and 3), much remains to be learned about the dual-function sRNA regulators. For example, the molecular functions of the proteins encoded by bifunctional sRNAs and the roles of these small proteins in cellular physiology are not well understood. Moreover, the interplay between translation and base-pairing activity has not been characterized for any dual-function sRNA. In this study, we use a dual-function sRNA from Escherichia coli and Salmonella as a model for understanding how a single RNA can serve two mechanistically distinct purposes.SgrS is a bifunctional sRNA expressed during a specific metabolic stress condition called glucose-phosphate stress (4-6). This stress causes growth inhi...

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supporting

confidence: 81%

Deciphering the Interplay between Two Independent Functions of the Small RNA Regulator SgrS in Salmonella

Balasubramanian

Vanderpool

2013

J Bacteriol

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“…For example, a recent study showed that a Salmonella small noncoding RNA can discriminate mRNA regions that differ by a single nucleotide (44). The picture is more complex for ct058 and ct192.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in Inc Proteins and Differential Expression ofincGenes among Chlamydia trachomatis Strains Correlate with Invasiveness and Tropism of Lymphogranuloma Venereum Isolates

et al. 2012

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Chlamydia trachomatis is a human bacterial pathogen that multiplies only within an intracellular membrane-bound vacuole, the inclusion. C. trachomatis includes ocular and urogenital strains, usually causing infections restricted to epithelial cells of the conjunctiva and genital mucosa, respectively, and lymphogranuloma venereum (LGV) strains, which can infect macrophages and spread into lymph nodes. However, C. trachomatis genomes display >98% identity at the DNA level. In this work, we studied whether C. trachomatis Inc proteins, which have a bilobed hydrophobic domain that may mediate their insertion in the inclusion membrane, could be a factor determining these different types of infection and tropisms. Analyses of polymorphisms and phylogeny of 48 Inc proteins from 51 strains encompassing the three disease groups showed significant amino acid differences that were mainly due to variations between Inc proteins from LGV and ocular or urogenital isolates. Studies of the evolutionary dynamics of inc genes suggested that 10 of them are likely under positive selection and indicated that most nonsilent mutations are LGV specific. Additionally, real-time quantitative PCR analyses in prototype and clinical strains covering the three disease groups identified three inc genes with LGV-specific expression. We determined the transcriptional start sites of these genes and found LGV-specific nucleotides within their promoters. Thus, subtle variations in the amino acids of a subset of Inc proteins and in the expression of inc genes may contribute to the unique tropism and invasiveness of C. trachomatis LGV strains.

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“…It is clear from recent studies that there are numerous exceptions in both animals and bacteria to the localization of sRNA-binding sites in UTRs, and sites located within coding sequences of mRNAs have been verified (3,39). Moreover, it is becoming apparent that many conserved sRNAs may regulate distinct subsets of targets, namely, those that are conserved members of the sRNA's regulon and those that are regulated in some but not all of the organisms that possess that particular sRNA (9,40,41). Our study adds yet another layer of complexity to this issue.…”

Section: Discussionmentioning

confidence: 99%

Small RNA binding-site multiplicity involved in translational regulation of a polycistronic mRNA

Rice

Balasubramanian

Vanderpool

2012

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

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In animal systems, mRNAs subject to posttranscriptional regulation by small RNAs (sRNAs) often possess multiple binding sites with imperfect complementarity to a given sRNA. In contrast, small RNA-mRNA interactions in bacteria and plants typically involve a single binding site. In a previous study, we demonstrated that the Escherichia coli sRNA SgrS base pairs with a site in the coding region of the first gene of a polycistronic message, manXYZ. This interaction was shown to be responsible for translational repression of manX and to contribute to destabilization of the manXYZ mRNA. In the current study, we report that translational repression of the manY and manZ genes by SgrS requires a second binding site located in the manX-manY intergenic region. Pairing at this site can repress translation of manY and manZ even when mRNA degradation is blocked. Base pairing between SgrS and the manX site does not affect translation of manY or manZ. Pairing at both sites is required for optimal SgrS-mediated degradation of the fulllength manXYZ mRNA and for a particular stress phenotype. These results suggest that bacterial sRNAs may use target-site multiplicity to enhance the efficiency and stringency of regulation. Moreover, use of multiple binding sites may be particularly important for coordinating regulation of multiple genes encoded in operons.glucose-phosphate stress | Hfq | phosphoenolpyruvate phosphotransferase system | RNase E N ow accepted as fundamentally important players in regulation of gene expression, regulatory RNAs are present in organisms across all domains of life. In many eukaryotic organisms, siRNAs and microRNAs (miRNAs) control gene expression at the posttranscriptional level in diverse pathways (1-3). In bacteria, small RNAs (sRNAs) similarly control gene expression posttranscriptionally, and the principles (if not the details) of sRNA regulatory mechanisms have much in common with miRNA and siRNA regulation. Like miRNAs, many bacterial sRNAs function by base pairing with mRNA targets to affect their translation and stability. Both miRNAs and bacterial sRNAs usually regulate multiple mRNAs through interactions involving short regions (7-10 bases) of imperfect complementarity. In most instances, base pairing between sRNAs or miRNAs and their mRNA targets negatively affects target expression by modulating translation and mRNA stability (2, 4). Bacterial sRNAs usually repress target mRNA translation by base pairing with and sequestering sequences of the ribosome-binding site (RBS) in the 5′ UTR of the mRNA, making it unavailable for ribosome binding. Subsequent mRNA degradation is initiated by the endoribonuclease RNase E and its associated proteins, collectively referred to as the "degradosome" (4).SgrS is a well-studied sRNA found in enteric bacteria and is expressed in response to a metabolic stress known as "glucosephosphate" (GP) stress (5, 6). GP stress is a condition associated with imbalanced glycolytic flux resulting in the accumulation of sugar phosphates. The stress occurs when certain phosp...

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The ancestral SgrS RNA discriminates horizontally acquired Salmonella mRNAs through a single G-U wobble pair

Cited by 83 publications

References 66 publications

Deciphering the Interplay between Two Independent Functions of the Small RNA Regulator SgrS in Salmonella

Deciphering the Interplay between Two Independent Functions of the Small RNA Regulator SgrS in Salmonella

Polymorphisms in Inc Proteins and Differential Expression ofincGenes among Chlamydia trachomatis Strains Correlate with Invasiveness and Tropism of Lymphogranuloma Venereum Isolates

Small RNA binding-site multiplicity involved in translational regulation of a polycistronic mRNA

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