Regulation by Small RNAs in Bacteria: Expanding Frontiers

Storz, Gisela; Vogel, Jörg; Wassarman, Karen M.

doi:10.1016/j.molcel.2011.08.022

Cited by 1,060 publications

(1,083 citation statements)

References 111 publications

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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%

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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Section: Bacterial Srnasmentioning

confidence: 99%

Dual RNA-seq of pathogen and host

2012

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“…23 Consistently, Crich loop sequences are a common feature among sRNAs and it was postulated that these motifs generally are signatures of sRNAs that repress the translation of target mRNAs by pairing with the RBS. 24 An example is RNAIII, a sRNA which is predominant in Staphylococcus species.…”

Section: Resultsmentioning

confidence: 99%

Thermodynamic matchers for the construction of the cuckoo RNA family

Reinkensmeier

Giegerich

2015

RNA Biology

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RNA family models describe classes of functionally related, non-coding RNAs based on sequence and structure conservation. The most important method for modeling RNA families is the use of covariance models, which are stochastic models that serve in the discovery of yet unknown, homologous RNAs. However, the performance of covariance models in finding remote homologs is poor for RNA families with high sequence conservation, while for families with high structure but low sequence conservation, these models are difficult to built in the first place. A complementary approach to RNA family modeling involves the use of thermodynamic matchers. Thermodynamic matchers are RNA folding programs, based on the established thermodynamic model, but tailored to a specific structural motif. As thermodynamic matchers focus on structure and folding energy, they unfold their potential in discovering homologs, when high structure conservation is paired with low sequence conservation. In contrast to covariance models, construction of thermodynamic matchers does not require an input alignment, but requires human design decisions and experimentation, and hence, model construction is more laborious. Here we report a case study on an RNA family that was constructed by means of thermodynamic matchers. It starts from a set of known but structurally different members of the same RNA family. The consensus secondary structure of this family consists of 2 to 4 adjacent hairpins. Each hairpin loop carries the same motif, CCUCCUCCC, while the stems show high variability in their nucleotide content. The present study describes (1) a novel approach for the integration of the structurally varying family into a single RNA family model by means of the thermodynamic matcher methodology, and (2) provides the results of homology searches that were conducted with this model in a wide spectrum of bacterial species.

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“…Over the last decade, much has been learned about the complexity of bacterial gene expression and the different levels of regulation. Regulatory RNAs are increasingly being recognized as important players in many physiological and adaptive responses in pathogenic bacteria [18][19][20]. The first noncoding RNAs (ncRNAs) in L. monocytogenes were identified by coimmunoprecipitation with Hfq, a small RNA-binding protein required for the activity of small regulatory RNAs in prokaryotes [21] and by an in silico-based approaches [22].…”

Section: Unconventional Mechanisms Regulating Bacterial Gene Expressimentioning

confidence: 99%

How the Study of Listeria Monocytogenes has Led to New Concepts in Biology

Rolhion

Cossart

2017

Future Microbiol.

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The opportunistic intracellular bacterial pathogen Listeria monocytogenes has in 30 years emerged as an exceptional bacterial model system in infection biology. Research on this bacterium has provided considerable insight into how pathogenic bacteria adapt to mammalian hosts, invade eukaryotic cells, move intracellularly, interfere with host cell functions and disseminate within tissues. It also contributed to unveil features of normal host cells pathways and unsuspected functions of previously known cellular proteins. This review provides an updated overview of our knowledge on this pathogen. In many examples, findings on Listeria monocytogenes provided the basis for new concepts in bacterial regulation, cell biology and infection processes.

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Regulation by Small RNAs in Bacteria: Expanding Frontiers

Cited by 1,060 publications

References 111 publications

Dual RNA-seq of pathogen and host

Dual RNA-seq of pathogen and host

Thermodynamic matchers for the construction of the cuckoo RNA family

How the Study of Listeria Monocytogenes has Led to New Concepts in Biology

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