Bacterial Small RNA Regulators: Versatile Roles and Rapidly Evolving Variations

Gottesman, Susan; Storz, Gisela

doi:10.1101/cshperspect.a003798

Cited by 657 publications

(669 citation statements)

References 157 publications

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“…2). Second, the synonymous mutations could prevent binding of a small RNA (sRNA) targeting the gtsB transcript for degradation 27 . However, we found that deleting hfq, a protein required for the activity of many sRNAs 28 , did not decrease the elevated levels of gene expression associated with the synonymous mutations ( Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Adaptive synonymous mutations in an experimentally evolved Pseudomonas fluorescens population

2014

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Conventional wisdom holds that synonymous mutations, nucleotide changes that do not alter the encoded amino acid, have no detectable effect on phenotype or fitness. However, a growing body of evidence from both comparative and experimental studies suggests otherwise. Synonymous mutations have been shown to impact gene expression, protein folding and fitness, however, direct evidence that they can be positively selected, and so contribute to adaptation, is lacking. Here we report the recovery of two beneficial synonymous single base pair changes that arose spontaneously and independently in an experimentally evolved population of Pseudomonas fluorescens. We show experimentally that these mutations increase fitness by an amount comparable to non-synonymous mutations and that the fitness increases stem from increased gene expression. These results provide unequivocal evidence that synonymous mutations can drive adaptive evolution and suggest that this class of mutation may be underappreciated as a cause of adaptation and evolutionary dynamics.

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Section: Resultsmentioning

confidence: 99%

Adaptive synonymous mutations in an experimentally evolved Pseudomonas fluorescens population

2014

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“…The primary role of Hfq is to facilitate base pairing between sRNAs and target mRNAs to regulate their translation, mostly negatively and also positively in some cases (2,3). Another role of Hfq is to recruit RNase E near target mRNAs to destabilize sRNA-mRNA hybrids (14).…”

Section: Discussionmentioning

confidence: 99%

PolyU tail of rho-independent terminator of bacterial small RNAs is essential for Hfq action

Otaka

Ishikawa

Morita

et al. 2011

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

171

214

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Major bacterial small RNAs (sRNAs) regulate the translation and stability of target mRNAs through base pairing with the help of the RNA chaperone Hfq. The Hfq-dependent sRNAs consist of three basic elements, mRNA base-pairing region, Hfq-binding site, and rho-independent terminator. Although the base-pairing region and the terminator are well documented in many sRNAs, the Hfq-binding site is less well-defined except that Hfq binds RNA with a preference for AU-rich sequences. Here, we performed mutational and biochemical studies to define the sRNA site required for Hfq action using SgrS as a model sRNA. We found that shortening terminator polyU tail eliminates the ability of SgrS to bind to Hfq and to silence ptsG mRNA. We also demonstrate that the SgrS terminator can be replaced with any foreign rho-independent terminators possessing a polyU tail longer than 8 without losing the ability to silence ptsG mRNA in an Hfq-dependent manner. Moreover, we found that shortening the terminator polyU tail of several other sRNAs also eliminates the ability to bind to Hfq and to regulate target mRNAs. We conclude that the polyU tail of sRNAs is essential for Hfq action in general. The data also indicate that the terminator polyU tail plays a role in Hfq-dependent stabilization of sRNAs.riboregulation | RNA 3′ end | RNase E | RyhB

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“…1.1). Among them the class of sRNAs constitutes the largest and best-studied cohort, with representatives in all studied bacterial species (both Gram-negative and -positive) (Gottesman and Storz, 2011;Storz et al, 2011).…”

Section: Bacterial Srnasmentioning

confidence: 99%

“…Many sRNA genes show signs of horizontal transfer, but conservation studies are generally difficult as sequence constraints are limited and often the secondary structure defines functionality (Gottesman and Storz, 2011). In Salmonella, the most recent transcriptome-wide analysis has predicted the presence of close to 300 different sRNAs (Kroger et al, 2013).…”

Section: Bacterial Srnasmentioning

confidence: 99%

“…The resulting lncRNA products might simply represent byproducts of transcription and are typically rapidly degraded after synthesis (Clark et al, 2012). (Albrecht et al, 2010(Albrecht et al, , 2011Chabelskaya et al, 2014;Chao et al, 2012;Gong et al, 2011;Grieshaber et al, 2006;Mann et al, 2012;Moon et al, 2013;Ortega et al, 2012;PadalonBrauch et al, 2008;Pfeiffer et al, 2007) crRNA, (Bhaya et al, 2011;Heidrich and Vogel, 2013;Sampson et al, 2013;van der Oost et al, 2014) (Georg and Hess, 2011;Giangrossi et al, 2010;GonzaloAsensio et al, 2013;Gottesman and Storz, 2011;Lasa et al, 2011;Lee and Groisman, 2010;Padalon-Brauch et al, 2008;Sesto et al, 2013) circRNAs rare varies arise from the 3'-5' ligation of both ends of linear RNA molecules n. a. -- (Doose et al, 2013;Vicens and Cech, 2009) - (Conway et al, 2014;Weinberg et al, 2009) Carpenter et al, 2013;Gomez et al, 2013;Iiott et al, 2014;Imamura et al, 2014;Li et al, 2014;Rapicavoli et al, 2013) poly ( …”

Section: Eukaryotic Long Non-coding Rnas (Lncrnas)mentioning

confidence: 99%

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Dual RNA-seq of pathogen and host

2012

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SummaryThe infection of a eukaryotic host cell by a bacterial pathogen is one of the most intimate examples of cross-kingdom interactions in biology. Infection processes are highly relevant from both a basic research as well as a clinical point of view. Sophisticated mechanisms have evolved in the pathogen to manipulate the host response and vice versa host cells have developed a wide range of anti-microbial defense strategies to combat bacterial invasion and clear infections.However, it is this diversity and complexity that makes infection research so challenging to technically address as common approaches have either been optimized for bacterial or eukaryotic organisms. Instead, methods are required that are able to deal with the often dramatic discrepancy between host and pathogen with respect to various cellular properties and processes. One class of cellular macromolecules that exemplify this host-pathogen heterogeneity is given by their transcriptomes: Bacterial transcripts differ from their eukaryotic counterparts in many aspects that involve both quantitative and qualitative traits. The entity of RNA transcripts present in a cell is of paramount interest as it reflects the cell's physiological state under the given condition. Genome-wide transcriptomic techniques such as RNA-seq have therefore been used for single-organism analyses for several years, but their applicability has been limited for infection studies.The present work describes the establishment of a novel transcriptomic approach for infection biology which we have termed "Dual RNA-seq". Using this technology, it was intended to shed light particularly on the contribution of non-protein-encoding transcripts to virulence, as these classes have mostly evaded previous infection studies due to the lack of suitable methods. The performance of Dual RNA-seq was evaluated in an in vitro infection model based on the important facultative intracellular pathogen Salmonella enterica serovar Typhimurium and different human cell lines. Dual RNA-seq was found to be capable of capturing all major bacterial and human transcript classes and proved reproducible. During the course of these experiments, a previously largely uncharacterized bacterial small non-coding RNA (sRNA), referred to as STnc440, was identified as one of the most strongly induced genes in intracellular Salmonella.Interestingly, while inhibition of STnc440 expression has been previously shown to cause a virulence defect in different animal models of Salmonellosis, the underlying molecular mechanisms have remained obscure. Here, classical genetics, transcriptomics and biochemical assays proposed a complex model of Salmonella gene expression control that is orchestrated by this sRNA. In particular, STnc440 was found to be involved in the regulation of multiple bacterial target mRNAs by direct base pair interaction with consequences for Salmonella virulence and

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Bacterial Small RNA Regulators: Versatile Roles and Rapidly Evolving Variations

Cited by 657 publications

References 157 publications

Adaptive synonymous mutations in an experimentally evolved Pseudomonas fluorescens population

Adaptive synonymous mutations in an experimentally evolved Pseudomonas fluorescens population

PolyU tail of rho-independent terminator of bacterial small RNAs is essential for Hfq action

Dual RNA-seq of pathogen and host

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