The Experts below are selected from a list of 219 Experts worldwide ranked by ideXlab platform
Ronald R Breaker - One of the best experts on this subject based on the ideXlab platform.
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Evidence for Widespread Gene Control Function by the ydaO Riboswitch Candidate
Journal of bacteriology, 2010Co-Authors: Kirsten F Block, Ming C Hammond, Ronald R BreakerAbstract:Nearly all representatives of experimentally validated riboswitch classes in bacteria Control the expression of Genes for the transport or synthesis of key metabolic compounds. Recent findings have revealed that some riboswitches also regulate Genes involved in physiological changes, virulence, and stress responses. Many novel RNA motifs are being identified by using bioinformatics algorithms that search for conserved sequence and structural features located in intergenic regions. Some of these RNAs are likely to function as riboswitches for metabolites or signaling compounds, and confirmation of this function would reveal the basis of the Genetic Control of new regulons. Herein we describe the analysis of the ydaO riboswitch candidate, which represents one of the most widespread candidates remaining to be validated. These RNAs are common in Gram-positive bacteria, and their genomic associations with diverse Genes suggest that they sense a compound that signals broader physiological changes. We determined that the ydaO motif exhibits sequence- and structure-dependent Gene Control, and reporter assays indicate that its natural ligand is present even when cells are grown in defined media. A transposon-mediated knockout screen resulted in mutants with a dysregulated expression of Genes Controlled by the RNA motif. The mutations disrupt Genes that drastically modulate energy-Generating pathways, suggesting that the intracellular concentration of the ligand sensed by the ydaO motif is altered under these stress conditions.
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ligand binding and Gene Control characteristics of tandem riboswitches in bacillus anthracis
RNA, 2007Co-Authors: Rudiger Welz, Ronald R BreakerAbstract:Most riboswitches are composed of a single metabolite-binding aptamer and a single expression platform that function together to regulate Genes in response to changing metabolite concentrations. In rare instances, two aptamers or sometimes two complete riboswitches reside adjacent to each other in untranslated regions (UTRs) of mRNAs. We have examined an example of a tandem riboswitch in the Gram-positive bacterium Bacillus anthracis that includes two complete riboswitches for thiamine pyrophosphate (TPP). Unlike other complex riboswitch systems described recently, tandem TPP riboswitches do not exhibit cooperative ligand binding and do not detect two different types of metabolites. In contrast, both riboswitches respond independently to TPP and are predicted to function in concert to mimic the more “digital” Gene Control outcome observed when two aptamers bind ligands cooperatively. Our findings further demonstrate that simple Gene Control elements made only of RNA can be assembled in different architectures to yield more complex Gene Control outcomes.
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tandem riboswitch architectures exhibit complex Gene Control functions
Science, 2006Co-Authors: Narasimhan Sudarsan, Rudiger Welz, Ming C Hammond, Kirsten F Block, Jeffrey E Barrick, Adam Roth, Ronald R BreakerAbstract:Riboswitches are structured RNAs typically located in the 5′ untranslated regions of bacterial mRNAs that bind metabolites and Control Gene expression. Most riboswitches sense one metabolite and function as simple Genetic switches. However, we found that the 5′ region of the Bacillus clausii metE messenger RNA includes two riboswitches that respond to S -adenosylmethionine and coenzyme B12. This tandem arrangement yields a composite Gene Control system that functions as a two-input Boolean NOR logic gate. These findings and the discovery of additional tandem riboswitch architectures reveal how simple RNA elements can be assembled to make sophisticated Genetic decisions without involving protein factors.
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regulation of bacterial Gene expression by riboswitches
Annual Review of Microbiology, 2005Co-Authors: Wade C Winkler, Ronald R BreakerAbstract:AbstractRiboswitches are structured domains that usually reside in the noncoding regions of mRNAs, where they bind metabolites and Control Gene expression. Like their protein counterparts, these RNA Gene Control elements form highly specific binding pockets for the target metabolite and undergo allosteric changes in structure. Numerous classes of riboswitches are present in bacteria and they comprise a common and robust metabolite-sensing system.
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riboswitches as versatile Gene Control elements
Current Opinion in Structural Biology, 2005Co-Authors: Brian J Tucker, Ronald R BreakerAbstract:Riboswitches are structured elements typically found in the 5' untranslated regions of mRNAs, where they regulate Gene expression by binding to small metabolites. In all examples studied to date, these RNA Control elements do not require the involvement of protein factors for metabolite binding. Riboswitches appear to be pervasive in eubacteria, suggesting that this form of regulation is an important mechanism by which metabolic Genes are Controlled. Recently discovered riboswitch classes have surprisingly complex mechanisms for regulating Gene expression and new high-resolution structural models of these RNAs provide insight into the molecular details of metabolite recognition by natural RNA aptamers.
Megan E. Porter - One of the best experts on this subject based on the ideXlab platform.
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The Shigella virulence Gene regulatory cascade: a paradigm of bacterial Gene Control mechanisms
Molecular microbiology, 1998Co-Authors: Charles J. Dorman, Megan E. PorterAbstract:Shigella flexneri is the causative agent of bacillary dysentery and is a facultative intracellular pathogen. Its virulence regulon is subject to tight Control by several mechanisms involving the products of over 20 Genes and an array of environmental signals. The reguIon is carried on a plasmid that is prone to instability and to integration into the chromosome, with associated silencing of the virulence Genes. Closely related regulons are found in other species of Shigella and in enteroinvasive Escherichia coli. A wealth of detailed information is now available on the Shigella virulence Gene Control circuits, and it is becoming clear that these share many features with regulatory systems found in other bacterial pathogens. All of this makes the S. flexneri virulence Gene Control system a very attractive topic for those interested in the nature of Gene regulatory networks in bacteria.
Cecilia Nigro - One of the best experts on this subject based on the ideXlab platform.
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EpiGenetic modifications of the Zfp/ZNF423 Gene Control murine adipogenic commitment and are dysregulated in human hypertrophic obesity
Diabetologia, 2018Co-Authors: Michele Longo, Gregory A. Raciti, Federica Zatterale, Luca Parrillo, Antonella Desiderio, Rosa Spinelli, Ann Hammarstedt, Shahram Hedjazifar, Jenny M. Hoffmann, Cecilia NigroAbstract:Aims/hypothesis Subcutaneous adipocyte hypertrophy is associated with insulin resistance and increased risk of type 2 diabetes, and predicts its future development independent of obesity. In humans, subcutaneous adipose tissue hypertrophy is a consequence of impaired adipocyte precursor cell recruitment into the adipogenic pathway rather than a lack of precursor cells. The zinc finger transcription factor known as zinc finger protein (ZFP) 423 has been identified as a major determinant of pre-adipocyte commitment and maintained white adipose cell function. Although its levels do not change during adipoGenesis, ectopic expression of Zfp423 in non-adipogenic murine cells is sufficient to activate expression of the Gene encoding peroxisome proliferator-activated receptor γ ( Pparγ ; also known as Pparg ) and increase the adipogenic potential of these cells. We investigated whether the Zfp423 Gene is under epiGenetic regulation and whether this plays a role in the restricted adipoGenesis associated with hypertrophic obesity. Methods Murine 3T3-L1 and NIH-3T3 cells were used as fibroblasts committed and uncommitted to the adipocyte lineage, respectively. Human pre-adipocytes were isolated from the stromal vascular fraction of subcutaneous adipose tissue of 20 lean non-diabetic individuals with a wide adipose cell size range. mRNA levels were measured by quantitative real-time PCR, while methylation levels were analysed by bisulphite sequencing. Chromatin structure was analysed by micrococcal nuclease protection assay, and DNA-methyltransferases were chemically inhibited by 5-azacytidine. Adipocyte differentiation rate was evaluated by Oil Red O staining. Results Comparison of uncommitted (NIH-3T3) and committed (3T3-L1) adipose precursor cells revealed that Zfp423 expression increased ( p
Charles J. Dorman - One of the best experts on this subject based on the ideXlab platform.
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The Shigella virulence Gene regulatory cascade: a paradigm of bacterial Gene Control mechanisms
Molecular microbiology, 1998Co-Authors: Charles J. Dorman, Megan E. PorterAbstract:Shigella flexneri is the causative agent of bacillary dysentery and is a facultative intracellular pathogen. Its virulence regulon is subject to tight Control by several mechanisms involving the products of over 20 Genes and an array of environmental signals. The reguIon is carried on a plasmid that is prone to instability and to integration into the chromosome, with associated silencing of the virulence Genes. Closely related regulons are found in other species of Shigella and in enteroinvasive Escherichia coli. A wealth of detailed information is now available on the Shigella virulence Gene Control circuits, and it is becoming clear that these share many features with regulatory systems found in other bacterial pathogens. All of this makes the S. flexneri virulence Gene Control system a very attractive topic for those interested in the nature of Gene regulatory networks in bacteria.
Christophe Beloin - One of the best experts on this subject based on the ideXlab platform.
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Regulation of virulence Gene expression in Shigella flexneri, a facultative intracellular pathogen
International Journal of Medical Microbiology, 2001Co-Authors: Charles Dorman, Sorcha Mckenna, Christophe BeloinAbstract:Shigella flexneri and its close relatives are facultative intracellular pathogens of humans and are the etiological agents of bacillary dysentery. These bacteria secrete proteins that enable them to enter human epithelial cells via an elaborate and fascinating cell biology. This behaviour depends on a complicated regulon of virulence Genes, whose expression is Controlled in response to a multiplicity of environmental signals. This review describes and attempts to interpret these Gene Control mechanisms.