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Riboswitch OR Riboswitches

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https://www.readbyqxmd.com/read/29346617/riboswitching-with-ciprofloxacin-development-and-characterization-of-a-novel-rna-regulator
#1
Florian Groher, Cristina Bofill-Bosch, Christopher Schneider, Johannes Braun, Sven Jager, Katharina Geißler, Kay Hamacher, Beatrix Suess
RNA molecules play important and diverse regulatory roles in the cell. Inspired by this natural versatility, RNA devices are increasingly important for many synthetic biology applications, e.g. optimizing engineered metabolic pathways, gene therapeutics or building up complex logical units. A major advantage of RNA is the possibility of de novo design of RNA-based sensing domains via an in vitro selection process (SELEX). Here, we describe development of a novel ciprofloxacin-responsive riboswitch by in vitro selection and next-generation sequencing-guided cellular screening...
January 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29341438/natural-antisense-transcripts-in-diseases-from-modes-of-action-to-targeted-therapies
#2
REVIEW
Elżbieta Wanowska, Magdalena Regina Kubiak, Wojciech Rosikiewicz, Izabela Makałowska, Michał Wojciech Szcześniak
Antisense transcription is a widespread phenomenon in mammalian genomes, leading to production of RNAs molecules referred to as natural antisense transcripts (NATs). NATs apply diverse transcriptional and post-transcriptional regulatory mechanisms to carry out a wide variety of biological roles that are important for the normal functioning of living cells, but their dysfunctions can be associated with human diseases. In this review, we attempt to provide a molecular basis for the involvement of NATs in the etiology of human disorders such as cancers and neurodegenerative and cardiovascular diseases...
January 17, 2018: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/29311281/cyclic-di-gmp-regulates-tfoy-in-vibrio-cholerae-to-control-motility-by-both-transcriptional-and-posttranscriptional-mechanisms
#3
Benjamin R Pursley, Michael M Maiden, Meng-Lun Hsieh, Nicolas Fernandez, Geoffrey B Severin, Christopher M Waters
Cyclic di-GMP (c-di-GMP) is a bacterial second messenger molecule that is a key global regulator in Vibrio cholerae, but the molecular mechanisms by which this molecule regulates downstream phenotypes have not been fully characterized. One such regulatory factor that may respond to c-di-GMP is the Vc2 c-di-GMP-binding riboswitch that is hypothesized to control the expression of the downstream putative transcription factor TfoY. Although much is known about the physical and structural properties of the Vc2 riboswitch aptamer, the nature of its expression and function in V...
January 8, 2018: Journal of Bacteriology
https://www.readbyqxmd.com/read/29297679/rna-structural-dynamics-as-captured-by-molecular-simulations-a-comprehensive-overview
#4
Jiří Šponer, Giovanni Bussi, Miroslav Krepl, Pavel Banáš, Sandro Bottaro, Richard A Cunha, Alejandro Gil-Ley, Giovanni Pinamonti, Simón Poblete, Petr Jurečka, Nils G Walter, Michal Otyepka
With both catalytic and genetic functions, ribonucleic acid (RNA) is perhaps the most pluripotent chemical species in molecular biology, and its functions are intimately linked to its structure and dynamics. Computer simulations, and in particular atomistic molecular dynamics (MD), allow structural dynamics of biomolecular systems to be investigated with unprecedented temporal and spatial resolution. We here provide a comprehensive overview of the fast-developing field of MD simulations of RNA molecules. We begin with an in-depth, evaluatory coverage of the most fundamental methodological challenges that set the basis for the future development of the field, in particular, the current developments and inherent physical limitations of the atomistic force fields and the recent advances in a broad spectrum of enhanced sampling methods...
January 3, 2018: Chemical Reviews
https://www.readbyqxmd.com/read/29279370/single-molecule-fret-studies-on-the-cotranscriptional-folding-of-a-thiamine-pyrophosphate-riboswitch
#5
Heesoo Uhm, Wooyoung Kang, Kook Sun Ha, Changwon Kang, Sungchul Hohng
Because RNAs fold as they are being synthesized, their transcription rate can affect their folding. Here, we report the results of single-molecule fluorescence studies that characterize the ligand-dependent cotranscriptional folding of the Escherichia coli thiM riboswitch that regulates translation. We found that the riboswitch aptamer folds into the "off" conformation independent of its ligand, but switches to the "on" conformation during transcriptional pausing near the translational start codon. Ligand binding maintains the riboswitch in the off conformation during transcriptional pauses...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29235474/engineering-cell-signaling-using-tunable-crispr-cpf1-based-transcription-factors
#6
Yuchen Liu, Jinghong Han, Zhicong Chen, Hanwei Wu, Hongsong Dong, Guohui Nie
The catalytically dead Cpf1 endonuclease from Acidaminococcus sp. BV3L6 (dAsCpf1) has been used to construct effective transcriptional repressors in bacteria and plants. However, it is still unclear if dAsCpf1 can function in human cells as a transcriptional regulator or a signal conductor. Here, we repurpose the dAsCpf1 system in human cells for a variety of functions, including the activation or repression of gene transcription. Moreover, we construct programmable ligand-controlled dAsCpf1 systems either by coupling crRNAs with engineered riboswitches or by fusing dAsCpf1 proteins with G protein-coupled receptors...
December 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29227220/taxonomic-analyses-of-members-of-the-streptomyces-cinnabarinus-cluster-description-of-streptomyces-cinnabarigriseus-sp-nov-and-streptomyces-davaonensis-sp-nov
#7
Wiebke Landwehr, Peter Kämpfer, Stefanie P Glaeser, Christian Rückert, Jörn Kalinowski, Jochen Blom, Alexander Goesmann, Matthias Mack, Peter Schumann, Ewelina Atasayar, Richard L Hahnke, Manfred Rohde, Karin Martin, Marc Stadler, Joachim Wink
Roseoflavin is the only known riboflavin (vitamin B2) analog with antibiotic properties. It is actively taken up by many micro-organisms and targets flavinmononucleotide riboswitches and flavoproteins. It is described as the product of the tentatively named 'Streptomyces davawensis' JCM 4913. Taxonomic analysis of this strain with a polyphasic approach showed that it is very closely related to Streptomyces cinnabarinus (DSM 40467). The two Streptomyces isolates were obtained from different geographical locations (the Philippines and the Kamchatka Peninsula, respectively), their genomes have been sequenced and the question was whether or not the two isolates were representatives of the same species...
December 11, 2017: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/29223402/genetic-regulation-mechanism-of-the-yjdf-riboswitch
#8
Sha Gong, Yanli Wang, Zhen Wang, Yujie Wang, Wenbing Zhang
The yjdF riboswitch resides in potential 5' UTRs of homologues of protein-coding gene yjdF in Firmicutes. Unlike other 30 riboswitch classes previously validated, this riboswitch class, can sense and bind to a broad collection of azaaromatic ligands. Among these compounds, some do activate production of yjdF protein driven by the riboswitch, while others are out of riboswitch-mediated modulation possibly because of the toxicity at high ligand concentrations. By incorporating the structures with pseudoknots and ligand binding kinetics into the co-transcriptional folding theory, we theoretically studied the co-transcriptional folding behaviors of the yjdF riboswitch from Bacillus subtilis at different transcription conditions...
December 6, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29220796/purine-analogs-targeting-the-guanine-riboswitch-as-potential-antibiotics-against-clostridioides-difficile
#9
Lok-Hang Yan, Antoine Le Roux, Kumaraswamy Boyapelly, Anne-Marie Lamontagne, Marie-Ann Archambault, Frédéric Picard-Jean, David Lalonde-Seguin, Emilie St-Pierre, Rafael J Najmanovich, Louis-Charles Fortier, Daniel Lafontaine, Éric Marsault
Riboswitches recently emerged as possible targets for the development of alternative antimicrobial approaches. Guanine-sensing riboswitches in the bacterial pathogen Clostridioides difficile (formerly known as Clostridium difficile) constitute potential targets based on their involvement in the regulation of basal metabolic control of purine compounds. In this study, we deciphered the structure-activity relationship of several guanine derivatives on the guanine riboswitch and determined their antimicrobial activity...
December 2, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29211762/ribofacseq-a-new-method-for-investigating-metabolic-and-transport-pathways-in-bacterial-cells-by-combining-a-riboswitch-based-sensor-fluorescence-activated-cell-sorting-and-next-generation-sequencing
#10
Zohaib Ghazi, Shahrzad Jahanshahi, Yingfu Li
The elucidation of the cellular processes involved in vitamin and cofactor biosynthesis is a challenging task. The conventional approaches to these investigations rely on the discovery and purification of the products (i.e proteins and metabolites) of a particular transport or biosynthetic pathway, prior to their subsequent analysis. However, the purification of low-abundance proteins or metabolites is a formidable undertaking that presents considerable technical challenges. As a solution, we present an alternative approach to such studies that circumvents the purification step...
2017: PloS One
https://www.readbyqxmd.com/read/29191010/design-of-a-temperature-responsive-transcription-terminator
#11
Johanna Roßmanith, Mareen Weskamp, Franz Narberhaus
RNA structures regulate various steps in gene expression. Transcription in bacteria is typically terminated by stable hairpin structures. Translation initiation can be modulated by metabolite- or temperature-sensitive RNA structures, called riboswitches or RNA thermometers (RNATs), respectively. RNATs control translation initiation by occlusion of the ribosome binding site at low temperatures. Increasing temperatures destabilize the RNA structure and facilitate ribosome access. In this study, we exploited temperature-responsive RNAT structures to design regulatory elements that control transcription termination instead of translation initiation in Escherichia coli...
November 30, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/29180020/aptamers-in-bordeaux-2017-an-exceptional-mill%C3%A3-sime
#12
Jean-Jacques Toulmé, Laurent Azéma, Fabien Darfeuille, Eric Dausse, Guillaume Durand, Olivier Paurelle
About 150 participants attended the symposium organised at the Palais de la Bourse in Bordeaux, France on September 22-23, 2017. Thirty speakers from all over the world delivered lectures covering selection processes, aptamer chemistry and innovative applications of these powerful tools that display major advantages over antibodies. Beyond the remarkable science presented, lively discussion and fruitful exchange between participants made this meeting a great success. A series of lectures were focused on synthetic biology (riboswitches, new synthetic base pairs, mutated polymerases)...
November 24, 2017: Biochimie
https://www.readbyqxmd.com/read/29170966/a-capture-selex-strategy-for-multiplexed-selection-of-rna-aptamers-against-small-molecules
#13
Lasse H Lauridsen, Holger B Doessing, Katherine S Long, Alex T Nielsen
In vitro selection of aptamers that recognize small organic molecules has proven difficult, in part due to the challenge of immobilizing small molecules on solid supports for SELEX (Systematic Evolution of Ligands by Exponential Enrichment). This study describes the implementation of RNA Capture-SELEX, a selection strategy that uses an RNA library to yield ligand-responsive RNA aptamers targeting small organic molecules in solution. To demonstrate the power of this method we selected several aptamers with specificity towards either the natural sweetener rebaudioside A or the food-coloring agent carminic acid...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29149090/computational-methods-for-modeling-aptamers-and-designing-riboswitches
#14
REVIEW
Sha Gong, Yanli Wang, Zhen Wang, Wenbing Zhang
Riboswitches, which are located within certain noncoding RNA region perform functions as genetic "switches", regulating when and where genes are expressed in response to certain ligands. Understanding the numerous functions of riboswitches requires computation models to predict structures and structural changes of the aptamer domains. Although aptamers often form a complex structure, computational approaches, such as RNAComposer and Rosetta, have already been applied to model the tertiary (three-dimensional (3D)) structure for several aptamers...
November 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29138309/loss-of-popz-at-activity-in-agrobacterium-tumefaciens-by-deletion-or-depletion-leads-to-multiple-growth-poles-minicells-and-growth-defects
#15
Romain Grangeon, John Zupan, Yeonji Jeon, Patricia C Zambryski
Agrobacterium tumefaciens grows by addition of peptidoglycan (PG) at one pole of the bacterium. During the cell cycle, the cell needs to maintain two different developmental programs, one at the growth pole and another at the inert old pole. Proteins involved in this process are not yet well characterized. To further characterize the role of pole-organizing protein A. tumefaciens PopZ (PopZ At ), we created deletions of the five PopZ At domains and assayed their localization. In addition, we created a popZAt deletion strain (ΔpopZAt ) that exhibited growth and cell division defects with ectopic growth poles and minicells, but the strain is unstable...
November 14, 2017: MBio
https://www.readbyqxmd.com/read/29136199/site-specific-dual-color-labeling-of-long-rnas-for-single-molecule-spectroscopy
#16
Meng Zhao, Fabio D Steffen, Richard Börner, Michelle F Schaffer, Roland K O Sigel, Eva Freisinger
Labeling of long RNA molecules in a site-specific yet generally applicable manner is integral to many spectroscopic applications. Here we present a novel covalent labeling approach that is site-specific and scalable to long intricately folded RNAs. In this approach, a custom-designed DNA strand that hybridizes to the RNA guides a reactive group to target a preselected adenine residue. The functionalized nucleotide along with the concomitantly oxidized 3'-terminus can subsequently be conjugated to two different fluorophores via bio-orthogonal chemistry...
November 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29135333/challenges-of-ligand-identification-for-the-second-wave-of-orphan-riboswitch-candidates
#17
Etienne B Greenlee, Shira Stav, Ruben M Atilho, Kenneth I Brewer, Kimberly A Harris, Sarah N Malkowski, Gayan Mirihana Arachchilage, Kevin R Perkins, Madeline E Sherlock, Ronald R Breaker
Orphan riboswitch candidates are noncoding RNA motifs whose representatives are believed to function as genetic regulatory elements, but whose target ligands have yet to be identified. The study of certain orphans, particularly classes that have resisted experimental validation for many years, has led to the discovery of important biological pathways and processes once their ligands were identified. Previously, we highlighted details for four of the most common and intriguing orphan riboswitch candidates. This facilitated the validation of riboswitches for the signaling molecules c-di-AMP, ZTP, and ppGpp, the metal ion Mn(2+), and the metabolites guanidine and PRPP...
November 14, 2017: RNA Biology
https://www.readbyqxmd.com/read/29132120/rna-based-dynamic-genetic-controllers-development-strategies-and-applications
#18
REVIEW
Sungho Jang, Sungyeon Jang, Jina Yang, Sang Woo Seo, Gyoo Yeol Jung
Dynamic regulation of gene expression in response to various molecules is crucial for both basic science and practical applications. RNA is considered an attractive material for creating dynamic genetic controllers because of its specific binding to ligands, structural flexibility, programmability, and small size. Here, we review recent advances in strategies for developing RNA-based dynamic controllers and applications. First, we describe studies that re-engineered natural riboswitches to generate new dynamic controllers...
November 10, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29106607/rnomics-of-thermus-themophilus-hb8-by-dna-microarray-and-next-generation-sequencing
#19
Gota Kawai, Yuri Aoki, Maina Otsu, Naomi Koike, Gen-Ichi Sampei
By using the data obtained by the DNA microarray analysis for the intergenic regions applied to RNA samples extracted from Thermus thermophilus HB8, seven small non-coding RNAs, TtR-1 to TtR-7, were found to be expressed in the cells growing in rich and/or minimal media. By analysing the time course of the expression for the cell growth in combination with the sequence comparison to the known RNAs, two RNAs, TtR-1 and TtR-2, are suggested to be riboswitches. The existence of the seven RNAs and the exact sequence and length, ranging 77-284 nt, were confirmed by the next-generation sequencing...
July 4, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/29106323/sam-vi-rnas-selectively-bind-s-adenosylmethionine-and-exhibit-similarities-to-sam-iii-riboswitches
#20
Gayan Mirihana Arachchilage, Madeline E Sherlock, Zasha Weinberg, Ronald R Breaker
Five distinct riboswitch classes that regulate gene expression in response to the cofactor S-adenosylmethionine (SAM) or its metabolic breakdown product S-adenosylhomocysteine (SAH) have been reported previously. Collectively, these SAM- or SAH-sensing RNAs constitute the most abundant collection of riboswitches, and are found in nearly every major bacterial lineage. Here, we report a potential sixth member of this pervasive riboswitch family, called SAM-VI, which is predominantly found in Bifidobacterium species...
November 6, 2017: RNA Biology
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