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https://www.readbyqxmd.com/read/28333103/the-genetic-code-and-rna-amino-acid-affinities
#1
REVIEW
Michael Yarus
A significant part of the genetic code likely originated via a chemical interaction, which should be experimentally verifiable. One possible verification relates bound amino acids (or perhaps their activated congeners) and ribonucleotide sequences within cognate RNA binding sites. To introduce this interaction, I first summarize how amino acids function as targets for RNA binding. Then the experimental method for selecting relevant RNA binding sites is characterized. The selection method's characteristics are related to the investigation of the RNA binding site model treated at the outset...
March 23, 2017: Life
https://www.readbyqxmd.com/read/28265071/bioinformatic-analysis-of-riboswitch-structures-uncovers-variant-classes-with-altered-ligand-specificity
#2
Zasha Weinberg, James W Nelson, Christina E Lünse, Madeline E Sherlock, Ronald R Breaker
Riboswitches are RNAs that form complex, folded structures that selectively bind small molecules or ions. As with certain groups of protein enzymes and receptors, some riboswitch classes have evolved to change their ligand specificity. We developed a procedure to systematically analyze known riboswitch classes to find additional variants that have altered their ligand specificity. This approach uses multiple-sequence alignments, atomic-resolution structural information, and riboswitch gene associations. Among the discoveries are unique variants of the guanine riboswitch class that most tightly bind the nucleoside 2'-deoxyguanosine...
March 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28248966/a-magnesium-induced-triplex-pre-organizes-the-sam-ii-riboswitch
#3
Susmita Roy, Heiko Lammert, Ryan L Hayes, Bin Chen, Regan LeBlanc, T Kwaku Dayie, José N Onuchic, Karissa Y Sanbonmatsu
Our 13C- and 1H-chemical exchange saturation transfer (CEST) experiments previously revealed a dynamic exchange between partially closed and open conformations of the SAM-II riboswitch in the absence of ligand. Here, all-atom structure-based molecular simulations, with the electrostatic effects of Manning counter-ion condensation and explicit magnesium ions are employed to calculate the folding free energy landscape of the SAM-II riboswitch. We use this analysis to predict that magnesium ions remodel the landscape, shifting the equilibrium away from the extended, partially unfolded state towards a compact, pre-organized conformation that resembles the ligand-bound state...
March 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28239422/differential-regulation-of-riboflavin-supply-genes-in-vibrio-cholerae
#4
Ignacio Sepúlveda Cisternas, Alexia Torres, Andrés Fuentes Flores, Víctor Antonio García Angulo
BACKGROUND: Riboflavin is the precursor of important redox cofactors such as flavin mononucleotide (FMN) and flavin adenine dinucleotide, required for several biological processes. Vibrio cholerae, a pathogenic bacterium responsible for the cholera disease, possesses the ability to biosynthesize de novo as well as to uptake riboflavin through the riboflavin biosynthetic pathway (RBP) and the RibN importer, respectively. The intra-organism relationship between riboflavin biosynthesis and uptake functions has not been studied...
2017: Gut Pathogens
https://www.readbyqxmd.com/read/28225108/an-integrated-perspective-on-rna-aptamer-ligand-recognition-models-clearing-muddy-waters
#5
K McCluskey, J Carlos Penedo
Riboswitches are short RNA motifs that sensitively and selectively bind cognate ligands to modulate gene expression. Like protein receptor-ligand pairs, their binding dynamics are traditionally categorized as following one of two paradigmatic mechanisms: conformational selection and induced fit. In conformational selection, ligand binding stabilizes a particular state already present in the receptor's dynamic ensemble. In induced fit, ligand-receptor interactions enable the system to overcome the energetic barrier into a previously inaccessible state...
February 22, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28214735/rna-based-control-mechanisms-of-clostridium-difficile
#6
REVIEW
Olga Soutourina
Clostridium difficile (CD)-associated diarrhoea is currently the most prevalent nosocomial diarrhoea worldwide. Many characteristics of CD pathogenicity remain poorly understood. Recent data strongly indicate the importance of an RNA network for the control of gene expression in CD. More than 200 regulatory RNAs have been identified by deep sequencing and targeted approaches, including Hfq-dependent trans riboregulators, cis-antisense RNAs, CRISPR RNAs, and c-di-GMP-responsive riboswitches. These regulatory RNAs are involved in the control of major processes in the CD infection cycle, for example motility, biofilm formation, adhesion, sporulation, stress response, and defence against bacteriophages...
February 16, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/28212758/the-guanidine-riboswitch-a-poor-orphan-no-longer
#7
David M J Lilley
Riboswitches are widespread in the bacterial kingdom, where they regulate gene expression in response to different small molecules and ions. However, some remain orphans with no known endogenous ligand. Three recently published papers (Battaglia et al., 2017; Nelson et al., 2017; and Reiss et al., 2017) de-orphanize a widespread ykkC element, showing that it responds to guanidine and elaborating on how that response is mediated.
February 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28212376/the-legionella-pneumophila-genome-evolved-to-accommodate-multiple-regulatory-mechanisms-controlled-by-the-csra-system
#8
Tobias Sahr, Christophe Rusniok, Francis Impens, Giulia Oliva, Odile Sismeiro, Jean-Yves Coppée, Carmen Buchrieser
The carbon storage regulator protein CsrA regulates cellular processes post-transcriptionally by binding to target-RNAs altering translation efficiency and/or their stability. Here we identified and analyzed the direct targets of CsrA in the human pathogen Legionella pneumophila. Genome wide transcriptome, proteome and RNA co-immunoprecipitation followed by deep sequencing of a wild type and a csrA mutant strain identified 479 RNAs with potential CsrA interaction sites located in the untranslated and/or coding regions of mRNAs or of known non-coding sRNAs...
February 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28209633/gene-expression-control-by-bacillus-anthracis-purine-riboswitches
#9
Marion Kirchner, Sabine Schneider
In all kingdoms of life, cellular replication relies on the presence of nucleosides and nucleotides, the building blocks of nucleic acids and the main source of energy. In bacteria, the availability of metabolites sometimes directly regulates the expression of enzymes and proteins involved in purine salvage, biosynthesis and uptake through riboswitches. Riboswitches are located in bacterial mRNAs and can control gene expression by conformational changes in response to ligand binding. We have established an inverse reporter gene system in Bacillus subtilis that allows us to monitor riboswitch-controlled gene expression...
February 16, 2017: RNA
https://www.readbyqxmd.com/read/28206750/synthetic-riboswitches-from-plug-and-pray-toward-plug-and-play
#10
Maja Etzel, Mario Mörl
In synthetic biology, metabolic engineering, and gene therapy, there is a strong demand for orthogonal or externally controlled regulation of gene expression. Here, RNA-based regulatory devices represent a promising emerging alternative to proteins, allowing a fast and direct control of gene expression, as no synthesis of regulatory proteins is required. Besides programmable ribozyme elements controlling mRNA stability, regulatory RNA structures in untranslated regions are highly interesting for engineering approaches...
February 24, 2017: Biochemistry
https://www.readbyqxmd.com/read/28204648/ligand-modulated-folding-of-the-full-length-adenine-riboswitch-probed-by-nmr-and-single-molecule-fret-spectroscopy
#11
Sven Warhaut, Klara Rebecca Mertinkus, Philipp Höllthaler, Boris Fürtig, Mike Heilemann, Martin Hengesbach, Harald Schwalbe
No abstract text is available yet for this article.
February 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28202709/understanding-in-line-probing-experiments-by-modeling-cleavage-of-non-reactive-rna-nucleotides
#12
Vojtech Mlynsky, Giovanni Bussi
Ribonucleic acid (RNA) is involved in many regulatory and catalytic processes in the cell. The function of any RNA molecule is intimately related with its structure. In-line probing experiments provide valuable structural datasets for a variety of RNAs and are used to characterize conformational changes in riboswitches. However, the structural determinants that lead to differential reactivities in unpaired nucleotides have not been investigated yet. In this work we used a combination of theoretical approaches, i...
February 15, 2017: RNA
https://www.readbyqxmd.com/read/28143908/guanidine-throws-the-riboswitch
#13
Alexandra A Mushegian
A bacterial riboswitch responds to endogenously produced guanidine.
January 31, 2017: Science Signaling
https://www.readbyqxmd.com/read/28138060/rna-puzzles-round-iii-3d-rna-structure-prediction-of-five-riboswitches-and-one-ribozyme
#14
Zhichao Miao, Ryszard W Adamiak, Maciej Antczak, Robert T Batey, Alexander J Becka, Marcin Biesiada, Michał J Boniecki, Janusz Bujnicki, Shi-Jie Chen, Clarence Yu Cheng, Fang-Chieh Chou, Adrian R Ferré-D'Amaré, Rhiju Das, Wayne K Dawson, Ding Feng, Nikolay V Dokholyan, Stanisław Dunin-Horkawicz, Caleb Geniesse, Kalli Kappel, Wipapat Kladwang, Andrey Krokhotin, Grzegorz E Łach, François Major, Thomas H Mann, Marcin Magnus, Katarzyna Pachulska-Wieczorek, Dinshaw J Patel, Joseph A Piccirilli, Mariusz Popenda, Katarzyna J Purzycka, Aiming Ren, Greggory M Rice, John Santalucia, Joanna Sarzynska, Marta Szachniuk, Arpit Tandon, Jeremiah J Trausch, Siqi Tian, Jian Wang, Kevin M Weeks, Benfeard Williams, Yi Xiao, Xiaojun Xu, Dong Zhang, Tomasz Zok, Eric Westhof
RNA-Puzzles is a collective experiment in blind 3D RNA structure prediction. We report here a third round of RNA-Puzzles. Five puzzles, 4, 8, 12, 13, 14, all structures of riboswitch aptamers and puzzle 7, a ribozyme structure, are included in this round of the experiment. The riboswitch structures include biological binding sites for small molecules (S-adenosyl methionine, cyclic diadenosine monophosphate, 5-amino 4-imidazole carboxamide riboside 5'-triphosphate, glutamine) and proteins (YbxF) and one set describes large conformational changes between ligand-free and ligand-bound states; the Varkud satellite ribozyme is the most recently solved structure of a known large ribozyme...
January 30, 2017: RNA
https://www.readbyqxmd.com/read/28134517/nmr-structural-profiling-of-transcriptional-intermediates-reveals-riboswitch-regulation-by-metastable-rna-conformations
#15
Christina Helmling, Anna Wacker, Michael T Wolfinger, Ivo L Hofacker, Martin Hengesbach, Boris Fuertig, Harald Schwalbe
Gene repression induced by the formation of transcriptional terminators represents a prime example for the coupling of RNA synthesis, folding and regulation. In this context, mapping the changes in available conformational space of transcription intermediates during RNA synthesis is important to understand riboswitch function. A majority of riboswitches, an important class of small metabolite-sensing regulatory RNAs, act as transcriptional regulators, but the dependence of ligand binding and the subsequent allosteric conformational switch on mRNA transcript length has not yet been investigated...
January 30, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28121427/riboswitch-based-reversible-dual-color-sensor
#16
Svetlana V Harbaugh, Michael S Goodson, Kateri Dillon, Sarah Zabarnick, Nancy Kelley-Loughnane
Riboswitches are RNA-based 'sensors' that utilize chemically-induced structural changes in the 5'-untranslated region of mRNA to regulate expression of downstream genes. Coupling a specific riboswitch with a reporter gene system translates chemical detection by the cell into a quantifiable reporter protein signal. For the majority of reporter gene systems the readout signal is only expressed in the presence of the target analyte. This makes it difficult to determine the viability and localization of the uninduced biosensor when it is used for 'real-word' applications...
January 25, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28117671/aptamers-in-bordeaux-24-25-june-2016
#17
Jean-Jacques Toulmé, Paloma H Giangrande, Günter Mayer, Beatrix Suess, Frédéric Ducongé, Bruce Sullenger, Vittorio de Franciscis, Fabien Darfeuille, Eric Peyrin
The symposium covered the many different aspects of the selection and the characterization of aptamers as well as their application in analytical, diagnostic and therapeutic areas. Natural and artificial riboswitches were discussed. Recent advances for the design of mutated polymerases and of chemically modified nucleic acid bases that provide aptamers with new properties were presented. The power of aptamer platforms for multiplex analysis of biomarkers of major human diseases was described. The potential of aptamers for the treatment of cancer or cardiovascular diseases was also presented...
January 20, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28115631/ligand-binding-to-2-deoxyguanosine-sensing-riboswitch-in-metabolic-context
#18
Yong-Boum Kim, Anna Wacker, Karl von Laer, Vladimir V Rogov, Beatrix Suess, Harald Schwalbe
The mfl-riboswitch is a transcriptional off-switch, which down-regulates expression of subunit β of ribonucleotide reductase in Mesoplasma florum upon 2'-deoxyguanosine binding. We characterized binding of 2'-deoxyguanosine to the mfl-aptamer domain (WT aptamer) and a sequence-stabilized aptamer (MT aptamer) under in vitro and 'in-cell-like' conditions by isothermal titration calorimetry (ITC) and nuclear magnetic resonance (NMR) spectroscopy. 'In-cell-like' environment was simulated by Bacillus subtilis cell extract, in which both aptamers remained sufficiently stable to detect the resonances of structural elements and ligand binding in 2D NMR experiments...
January 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28115628/divalent-ion-competition-reveals-reorganization-of-an-rna-ion-atmosphere-upon-folding
#19
Robert J Trachman, David E Draper
Although RNA interactions with K(+) and Mg(2+) have been studied extensively, much less is known about the third most abundant cation in bacterial cells, putrescine(2+), and how RNA folding might be influenced by the three ions in combination. In a new approach, we have observed the competition between Mg(2+) and putrescine(2+) (in a background of K(+)) with native, partially unfolded and highly extended conformations of an adenine riboswitch aptamer. With the native state, putrescine(2+) is a weak competitor when the ratio of the excess Mg(2+) (which neutralizes phosphate charge) to RNA is very low, but becomes much more effective at replacing Mg(2+) as the excess Mg(2+) in the RNA ion atmosphere increases...
January 23, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28115596/osmium-tetroxide-as-a-probe-of-rna-structure
#20
Jing Zhang, Danbin Li, Jun Zhang, Dongrong Chen, Alastair I H Murchie
Structured RNAs have a central role in cellular function. The capability of structured RNAs to adopt fixed architectural structures or undergo dynamic conformational changes contributes to their diverse role in the regulation of gene expression. Although numerous biophysical and biochemical tools have been developed to study structured RNAs, there is a continuing need for the development of new methods for the investigation of RNA structures, especially methods that allow RNA structure to be studied in solution close to its native cellular conditions...
April 2017: RNA
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