The ViennaRNA Web Services

Gruber, Andreas; Bernhart, Stephan H.; Lorenz, Ronny

doi:10.1007/978-1-4939-2291-8_19

Cited by 151 publications

(118 citation statements)

References 27 publications

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“…GMP synthetase (guaA) is a glutamine amidotransferase that converts XMP to GMP, after which GMP kinase (gmk) and ribonucleotide reductases (nrdIEF) generate dGDP. showing the three-junction stem-loop structure typical of the purine riboswitch aptamer (56). Nucleotides are highlighted to show stem (blue), loop (yellow), and bases conserved in guanine-binding riboswitches (red) (4,22).…”

Section: Resultsmentioning

confidence: 99%

De Novo Guanine Biosynthesis but Not the Riboswitch-Regulated Purine Salvage Pathway Is Required for Staphylococcus aureus Infection In Vivo

Kofoed¹,

Yan²,

Katakam³

et al. 2016

J Bacteriol

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De novo guanine biosynthesis is an evolutionarily conserved pathway that creates sufficient nucleotides to support DNA replication, transcription, and translation. Bacteria can also salvage nutrients from the environment to supplement the de novo pathway, but the relative importance of either pathway during Staphylococcus aureus infection is not known. In S. aureus, genes important for both de novo and salvage pathways are regulated by a guanine riboswitch. Bacterial riboswitches have attracted attention as a novel class of antibacterial drug targets because they have high affinity for small molecules, are absent in humans, and regulate the expression of multiple genes, including those essential for cell viability. Genetic and biophysical methods confirm the existence of a bona fide guanine riboswitch upstream of an operon encoding xanthine phosphoribosyltransferase (xpt), xanthine permease (pbuX), inosine-5=-monophosphate dehydrogenase (guaB), and GMP synthetase (guaA) that represses the expression of these genes in response to guanine. We found that S. aureus guaB and guaA are also transcribed independently of riboswitch control by alternative promoter elements. Deletion of xpt-pbuX-guaB-guaA genes resulted in guanine auxotrophy, failure to grow in human serum, profound abnormalities in cell morphology, and avirulence in mouse infection models, whereas deletion of the purine salvage genes xpt-pbuX had none of these effects. Disruption of guaB or guaA recapitulates the xpt-pbuXguaB-guaA deletion in vivo. In total, the data demonstrate that targeting the guanine riboswitch alone is insufficient to treat S. aureus infections but that inhibition of guaA or guaB could have therapeutic utility. IMPORTANCEDe novo guanine biosynthesis and purine salvage genes were reported to be regulated by a guanine riboswitch in Staphylococcus aureus. We demonstrate here that this is not true, because alternative promoter elements that uncouple the de novo pathway from riboswitch regulation were identified. We found that in animal models of infection, the purine salvage pathway is insufficient for S. aureus survival in the absence of de novo guanine biosynthesis. These data suggest targeting the de novo guanine biosynthesis pathway may have therapeutic utility in the treatment of S. aureus infections.

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Section: Resultsmentioning

confidence: 99%

De Novo Guanine Biosynthesis but Not the Riboswitch-Regulated Purine Salvage Pathway Is Required for Staphylococcus aureus Infection In Vivo

Kofoed¹,

Yan²,

Katakam³

et al. 2016

J Bacteriol

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“…An lncRNA harboring a miRNA precursor sequence with 100% query coverage and similarity was considered as precursor of that miRNA. The hairpin loop formation in lncRNAs was analyzed using miRNAFold server (https://evryrna.ibisc.univ-evry.fr/miRNAFold; Tav et al, 2016), and secondary structure was plotted using Vienna RNAfold web server (http://rna.tbi.univie.ac.at/; Gruber et al, 2015). …”

Section: Methodsmentioning

confidence: 99%

Survey of High Throughput RNA-Seq Data Reveals Potential Roles for lncRNAs during Development and Stress Response in Bread Wheat

et al. 2017

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Long non-coding RNAs (lncRNAs) are a family of regulatory RNAs that play essential role in the various developmental processes and stress responses. Recent advances in sequencing technology and computational methods enabled identification and characterization of lncRNAs in certain plant species, but they are less known in Triticum aestivum (bread wheat). Herein, we analyzed 52 RNA seq data (>30 billion reads) and identified 44,698 lncRNAs in T. aestivum genome, which were characterized in comparison to the coding sequences (mRNAs). Similar to the mRNAs, lncRNAs were also derived from each sub-genome and chromosome, and showed tissue developmental stage specific and differential expression, as well. The modulated expression of lncRNAs during abiotic stresses like heat, drought, and salt indicated their putative role in stress response. The co-expression of lncRNAs with vital mRNAs including various transcription factors and enzymes involved in Abscisic acid (ABA) biosynthesis, and gene ontology mapping inferred their regulatory roles in numerous biological processes. A few lncRNAs were predicted as precursor (19 lncRNAs), while some as target mimics (1,047 lncRNAs) of known miRNAs involved in various regulatory functions. The results suggested numerous functions of lncRNAs in T. aestivum, and unfolded the opportunities for functional characterization of individual lncRNA in future studies.

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“…While all of the programs implemented in this study utilize the same free-energy database, the way that multibranch loops are predicted varies in different RNA structure prediction programs. The prediction may consider all possible conformations of coaxial stacking, include only the single most favorable coaxial stacking arrangement, or include knowledge-based parameters from analysis of known secondary structures (Mathews et al 2004;Andronescu et al 2010;Gruber et al 2015;Kennedy 2016). None of the algorithms was able to account for the magnitude of differences observed among the measured stabilities of the investigated 3WJs.…”

Section: Future Improvements In Predicting Rna 3wj Stabilitiesmentioning

confidence: 99%

Thermodynamic stabilities of three-way junction nanomotifs in prohead RNA

Hill

Schroeder

2017

RNA

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The thermodynamic stabilities of four natural prohead or packaging RNA (pRNA) three-way junction (3WJ) nanomotifs and seven phi29 pRNA 3WJ deletion mutant nanomotifs were investigated using UV optical melting on a three-component RNA system. Our data reveal that some pRNA 3WJs are more stable than the phi29 pRNA 3WJ. The stability of the 3WJ contributes to the unique self-assembly properties of pRNA. Thus, ultrastable pRNA 3WJ motifs suggest new scaffolds for pRNA-based nanotechnology. We present data demonstrating that pRNA 3WJs differentially respond to the presence of metal ions. A comparison of our data with free energies predicted by currently available RNA secondary structure prediction programs shows that these programs do not accurately predict multibranch loop stabilities. These results will expand the existing parameters used for RNA secondary structure prediction from sequence in order to better inform RNA structure-function hypotheses and guide the rational design of functional RNA supramolecular assemblies.

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The ViennaRNA Web Services

Cited by 151 publications

References 27 publications

De Novo Guanine Biosynthesis but Not the Riboswitch-Regulated Purine Salvage Pathway Is Required for Staphylococcus aureus Infection In Vivo

De Novo Guanine Biosynthesis but Not the Riboswitch-Regulated Purine Salvage Pathway Is Required for Staphylococcus aureus Infection In Vivo

Survey of High Throughput RNA-Seq Data Reveals Potential Roles for lncRNAs during Development and Stress Response in Bread Wheat

Thermodynamic stabilities of three-way junction nanomotifs in prohead RNA

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