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https://www.readbyqxmd.com/read/28640851/ligand-mediated-and-tertiary-interactions-cooperatively-stabilize-the-p1-region-in-the-guanine-sensing-riboswitch
#1
Christian A Hanke, Holger Gohlke
Riboswitches are genetic regulatory elements that control gene expression depending on ligand binding. The guanine-sensing riboswitch (Gsw) binds ligands at a three-way junction formed by paired regions P1, P2, and P3. Loops L2 and L3 cap the P2 and P3 helices and form tertiary interactions. Part of P1 belongs to the switching sequence dictating the fate of the mRNA. Previous studies revealed an intricate relationship between ligand binding and presence of the tertiary interactions, and between ligand binding and influence on the P1 region...
2017: PloS One
https://www.readbyqxmd.com/read/28640671/regulation-of-a-muralytic-enzyme-encoding-gene-by-two-non-coding-rnas
#2
Renée J St-Onge, Marie A Elliot
Non-coding regulatory RNAs fine-tune gene expression post-transcriptionally. In the streptomycetes, rpfA - encoding a muralytic enzyme required for establishing and exiting dormancy - is flanked by non-coding regulatory RNA elements both upstream (riboswitch) and downstream [antisense small RNA (sRNA)]. In Streptomyces coelicolor, the upstream riboswitch decreases rpfA transcript abundance in response to the second messenger cyclic di-AMP, itself involved in cell wall metabolism and dormancy. There is, however, no obvious expression platform associated with this riboswitch and consequently, its mechanism of action is entirely unknown...
June 22, 2017: RNA Biology
https://www.readbyqxmd.com/read/28625696/comparative-visualization-of-the-rna-suboptimal-conformational-ensemble-in%C3%A2-vivo
#3
Chanin T Woods, Lela Lackey, Benfeard Williams, Nikolay V Dokholyan, David Gotz, Alain Laederach
When a ribonucleic acid (RNA) molecule folds, it often does not adopt a single, well-defined conformation. The folding energy landscape of an RNA is highly dependent on its nucleotide sequence and molecular environment. Cellular molecules sometimes alter the energy landscape, thereby changing the ensemble of likely low-energy conformations. The effects of these energy landscape changes on the conformational ensemble are particularly challenging to visualize for large RNAs. We have created a robust approach for visualizing the conformational ensemble of RNAs that is well suited for in vitro versus in vivo comparisons...
June 15, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28621923/capture-and-release-of-trna-by-the-t-loop-receptor-in-the-function-of-the-t-box-riboswitch
#4
Xianyang Fang, Malgorzata Michnicka, Yikan Zhang, Yun Xing Wang, Edward P Nikonowicz
In Gram-positive bacteria, the tRNA-dependent T-box riboswitch system regulates expression of amino acid biosynthetic and aminoacyl-tRNA synthetase genes through a transcription attenuation mechanism. Binding of uncharged tRNA "closes" the switch, allowing transcription read-through. Structure studies of the 100 nt stem I domain reveal tRNA utilizes base pairing and stacking interactions to bind the stem, but little is known structurally about the 180 nt riboswitch core (stem I, stem III, and antiterminator stem) in complex with tRNA and the mechanism of coupling of the intermolecular binding domains crucial to T-box function...
June 16, 2017: Biochemistry
https://www.readbyqxmd.com/read/28613837/artificial-off-riboswitches-that-downregulate-internal-ribosome-entry-without-hybridization-switches-in-a-eukaryotic-cell-free-translation-system
#5
Atsushi Ogawa, Hiroki Masuoka, Tsubasa Ota
We constructed novel artificial riboswitches that function in a eukaryotic translation system (wheat germ extract), by rationally implanting an in vitro-selected aptamer into the intergenic internal ribosome entry site (IRES) of Plautia stali intestine virus. These eukaryotic OFF-riboswitches (OFF-eRSs) ligand-dose-dependently downregulate IRES-mediated translation without hybridization switches, which typical riboswitches utilize for gene regulation. The hybridization-switch-free mechanism not only allows for easy design but also requires less energy for regulation, resulting in a higher switching efficiency than hybridization-switch-based OFF-eRSs provide...
June 14, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28611182/the-lost-language-of-the-rna-world
#6
REVIEW
James W Nelson, Ronald R Breaker
The possibility of an RNA World is based on the notion that life on Earth passed through a primitive phase without proteins, a time when all genomes and enzymes were composed of ribonucleic acids. Numerous apparent vestiges of this ancient RNA World remain today, including many nucleotide-derived coenzymes, self-processing ribozymes, metabolite-binding riboswitches, and even ribosomes. Many of the most common signaling molecules and second messengers used by modern organisms are also formed from RNA nucleotides or their precursors...
June 13, 2017: Science Signaling
https://www.readbyqxmd.com/read/28609710/sense-and-sensitivity-in-bioprocessing-detecting-cellular-metabolites-with-biosensors
#7
REVIEW
Linda Dekker, Karen M Polizzi
Biosensors use biological elements to detect or quantify an analyte of interest. In bioprocessing, biosensors are employed to monitor key metabolites. There are two main types: fully biological systems or biological recognition coupled with physical/chemical detection. New developments in chemical biosensors include multiplexed detection using microfluidics. Synthetic biology can be used to engineer new biological biosensors with improved characteristics. Although there have been few biosensors developed for bioprocessing thus far, emerging trends can be applied in the future...
June 10, 2017: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/28600356/structural-basis-for-ligand-binding-to-the-guanidine-ii-riboswitch
#8
Caroline W Reiss, Scott A Strobel
The guanidine-II riboswitch, also known as mini-ykkC, is a conserved mRNA element with more than 800 examples in bacteria. It consists of two stemloops capped by identical, conserved tetraloops that are separated by a linker region of variable length and sequence. Like the guanidine-I riboswitch, it controls the expression of guanidine carboxylases and SugE-like genes. The guanidine-II riboswitch specifically binds free guanidinium cation and functions as a translationally-controlled on-switch. Here we report the structure of a P2 stemloop from the Pseudomonas aeruginosa guanidine-II riboswitch aptamer bound to guanidine at 1...
June 9, 2017: RNA
https://www.readbyqxmd.com/read/28591515/roc-n-ribo-characterizing-a-riboswitching-expression-system-by-modeling-single-cell-data
#9
Christopher Schneider, Leo Bronstein, Jascha Diemer, Heinz Koeppl, Beatrix Suess
RNA-engineered systems offer simple and versatile control over gene expression in many organisms. In particular, the design and implementation of riboswitches presents a unique opportunity to manipulate any reporter device in cis, executing tight temporal and spatial control at low metabolic costs. Assembled to higher order genetic circuits, such riboswitch-regulated devices may efficiently process logical operations. Here, we propose a hierarchical stochastic modeling approach to characterize an in silico repressor gate based on neomycin- and tetracycline-sensitive riboswitches...
June 7, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28572834/stream-formula-see-text-algorithms-for-analyzing-coarse-grained-rna-dynamics-based-on-markov-models-of-connectivity-graphs
#10
Sven Jager, Benjamin Schiller, Philipp Babel, Malte Blumenroth, Thorsten Strufe, Kay Hamacher
BACKGROUND: In this work, we present a new coarse grained representation of RNA dynamics. It is based on adjacency matrices and their interactions patterns obtained from molecular dynamics simulations. RNA molecules are well-suited for this representation due to their composition which is mainly modular and assessable by the secondary structure alone. These interactions can be represented as adjacency matrices of k nucleotides. Based on those, we define transitions between states as changes in the adjacency matrices which form Markovian dynamics...
2017: Algorithms for Molecular Biology: AMB
https://www.readbyqxmd.com/read/28559057/synthesis-and-evaluation-of-c-di-4-thioamp-as-an-artificial-ligand-for-c-di-amp-riboswitch
#11
Kazuto Shiraishi, Noriko Saito-Tarashima, Yosuke Igata, Keiji Murakami, Yasuko Okamoto, Yoichiro Miyake, Kazuhiro Furukawa, Noriaki Minakawa
Cyclic-di-adenosine monophosphate (c-di-AMP) is a bacterial second messenger that binds to an RNA receptor called riboswitch and regulates its downstream genes involving cell wall metabolism, ion transport, and spore germination. Therefore, the c-di-AMP riboswitch can be a novel target of antibiotics. In this study, we synthesized c-di-4'-thioAMP (1), which possesses a sulfur atom instead of an oxygen atom in the furanose ring, as a candidate of a bioisoster for natural c-di-AMP. The resulting 1 bound to the c-di-AMP riboswitch with a micromolar affinity (34...
May 20, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28552565/production-of-amino-acids-genetic-and-metabolic-engineering-approaches
#12
REVIEW
Jin-Ho Lee, Volker F Wendisch
The biotechnological production of amino acids occurs at the million-ton scale and annually about 6milliontons of l-glutamate and l-lysine are produced by Escherichia coli and Corynebacterium glutamicum strains. l-glutamate and l-lysine production from starch hydrolysates and molasses is very efficient and access to alternative carbon sources and new products has been enabled by metabolic engineering. This review focusses on genetic and metabolic engineering of amino acid producing strains. In particular, rational approaches involving modulation of transcriptional regulators, regulons, and attenuators will be discussed...
May 15, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28543037/naringenin-responsive-riboswitch-based-fluorescent-biosensor-module-for-escherichia-coli-co-cultures
#13
Yu Xiu, Sungho Jang, J Andrew Jones, Nicholas A Zill, Robert J Linhardt, Qipeng Yuan, Gyoo Yeol Jung, Mattheos A G Koffas
The ability to design and construct combinatorial synthetic metabolic pathways has far exceeded our capacity for efficient screening and selection of the resulting microbial strains. The need for high-throughput rapid screening techniques is of upmost importance for the future of synthetic biology and metabolic engineering. Here we describe the development of a RNA riboswitch-based biosensor module with dual fluorescent reporters, and demonstrate a high-throughput flow cytometry-based screening method for identification of naringenin over producing Escherichia coli strains in co-culture...
May 20, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28541183/pausing-guides-rna-folding-to-populate-transiently-stable-rna-structures-for-riboswitch-based-transcription-regulation
#14
Hannah Steinert, Florian Sochor, Anna Wacker, Janina Buck, Christina Helmling, Fabian Hiller, Sara Keyhani, Jonas Noeske, Steffen Grimm, Martin M Rudolph, Heiko Keller, Rachel Anne Mooney, Robert Landick, Beatrix Suess, Boris Fürtig, Jens Wöhnert, Harald Schwalbe
In bacteria, the regulation of gene expression by cis-acting transcriptional riboswitches located in the 5'-untranslated regions of messenger RNA requires the temporal synchronization of RNA synthesis and ligand binding-dependent conformational refolding. Ligand binding to the aptamer domain of the riboswitch induces premature termination of the mRNA synthesis of ligand-associated genes due to the coupled formation of 3'-structural elements acting as terminators. To date, there has been no high resolution structural description of the concerted process of synthesis and ligand-induced restructuring of the regulatory RNA element...
May 25, 2017: ELife
https://www.readbyqxmd.com/read/28531275/molecular-envelope-and-atomic-model-of-an-anti-terminated-glyqs-t-box-regulator-in-complex-with-trnagly
#15
Bhaskar Chetnani, Alfonso Mondragón
A T-box regulator or riboswitch actively monitors the levels of charged/uncharged tRNA and participates in amino acid homeostasis by regulating genes involved in their utilization or biosynthesis. It has an aptamer domain for cognate tRNA recognition and an expression platform to sense the charge state and modulate gene expression. These two conserved domains are connected by a variable linker that harbors additional secondary structural elements, such as Stem III. The structural basis for specific tRNA binding is known, but the structural basis for charge sensing and the role of other elements remains elusive...
May 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28529506/roles-of-regulatory-rnas-for-antibiotic-resistance-in-bacteria-and-their-potential-value-as-novel-drug-targets
#16
REVIEW
Petra Dersch, Muna A Khan, Sabrina Mühlen, Boris Görke
The emergence of antibiotic resistance mechanisms among bacterial pathogens increases the demand for novel treatment strategies. Lately, the contribution of non-coding RNAs to antibiotic resistance and their potential value as drug targets became evident. RNA attenuator elements in mRNA leader regions couple expression of resistance genes to the presence of the cognate antibiotic. Trans-encoded small RNAs (sRNAs) modulate antibiotic tolerance by base-pairing with mRNAs encoding functions important for resistance such as metabolic enzymes, drug efflux pumps, or transport proteins...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28529131/the-structure-of-the-guanidine-ii-riboswitch
#17
Lin Huang, Jia Wang, David M J Lilley
The guanidine-II (mini-ykkC) riboswitch is the smallest of the guanidine-responsive riboswitches, comprising two stem loops of similar sequence. We have solved high-resolution crystal structures of both stem loops for the riboswitch from Gloeobacter violaceus. The stem loops have a strong propensity to dimerize by intimate loop-loop interaction. The dimerization creates specific binding pockets for two guanidine molecules, explaining their cooperative binding. Within the binding pockets the ligands are hydrogen bonded to a guanine at O6 and N7, and to successive backbone phosphates...
May 18, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28525764/two-are-better-than-one-dual-targeting-of-riboswitches-by-metabolite-analogs
#18
Stefanie Sandra Krajewski, Dmitry Ignatov, Jörgen Johansson
In this issue of Cell Chemical Biology, Wang et al. (2017) examine the effect of the novel synthetic molecule ribocil-C and the natural compound roseoflavin in Gram-positive pathogens. In methicillin-resistant Staphylococcus aureus (MRSA), ribocil-C and roseoflavin target two autonomous riboswitches simultaneously, thereby inhibiting de novo synthesis and uptake of riboflavin.
May 18, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28520932/translational-control-and-rho-dependent-transcription-termination-are-intimately-linked-in-riboswitch-regulation
#19
Laurène Bastet, Adrien Chauvier, Navjot Singh, Antony Lussier, Anne-Marie Lamontagne, Karine Prévost, Eric Massé, Joseph T Wade, Daniel A Lafontaine
Riboswitches are regulatory elements that control gene expression by altering RNA structure upon the binding of specific metabolites. Although Bacillus subtilis riboswitches have been shown to control premature transcription termination, less is known about regulatory mechanisms employed by Escherichia coli riboswitches, which are predicted to regulate mostly at the level of translation initiation. Here, we present experimental evidence suggesting that the majority of known E. coli riboswitches control transcription termination by using the Rho transcription factor...
May 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28504865/real-time-crystallographic-studies-of-the-adenine-riboswitch-using-an-x-ray-free-electron-laser
#20
REVIEW
J R Stagno, Y R Bhandari, C E Conrad, Y Liu, Y-X Wang
Structures of the four reaction states of the adenine riboswitch aptamer domain, including a transient intermediate state were solved by serial femtosecond crystallography. The structures not only demonstrate the use of X-ray free electron lasers for RNA crystallography but have also proven that transient states can be determined in real time by mix-and-inject crystallography. These results illustrate the structural basis for the ligand-induced conformational changes associated with the molecular "switch". This article is protected by copyright...
May 15, 2017: FEBS Journal
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