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Riboswitch OR Riboswitches

Keunsub Lee, Kan Wang
During the last decade, small noncoding RNAs (ncRNAs) have emerged as essential post-transcriptional regulators in bacteria. Nearly all important physiological and stress responses are modulated by ncRNA regulators, such as riboswitches, trans-acting small RNAs (sRNAs), and cis-antisense RNAs. Recently, three RNA-seq studies identified a total of 1534 candidate ncRNAs from Agrobacterium tumefaciens, a pathogen and biotechnology tool for plants. Only a few ncRNAs have been functionally characterized in A. tumefaciens, and some of them appear to be involved in virulence...
March 20, 2018: Current Topics in Microbiology and Immunology
Mikhail A Moldovan, Svetlana A Petrova, Mikhail S Gelfand
Riboswitches are conserved RNA structures located in non-coding regions of mRNA and able to bind small molecules (e.g. metabolites) changing conformation upon binding. This feature enables them to function as regulators of gene expression. The thiamin pyrophosphate (TPP) riboswitch is the only type of riboswitches found not only in bacteria, but also in eukaryotes - in plants, green algae, protists, and fungi. Two main mechanisms of fungal TPP riboswitch action, involving alternative splicing, have been established so far...
March 13, 2018: Fungal Genetics and Biology: FG & B
Laurène Bastet, Pierre Turcotte, Joseph T Wade, Daniel A Lafontaine
Riboswitches are RNA regulators that control gene expression by modulating their structure in response to metabolite binding. The study of mechanisms by which riboswitches modulate gene expression is crucial to understand how riboswitches are involved in maintaining cellular homeostasis. Previous reports indicate that riboswitches can control gene expression at the level of translation, transcription or mRNA decay. However, there are very few described examples where riboswitches regulate multiple steps in gene expression...
March 14, 2018: RNA Biology
Ping Ge, Shahidul Islam, Cuncong Zhong, Shaojie Zhang
As functional components in three-dimensional (3D) conformation of an RNA, the RNA structural motifs provide an easy way to associate the molecular architectures with their biological mechanisms. In the past years, many computational tools have been developed to search motif instances by using the existing knowledge of well-studied families. Recently, with the rapidly increasing number of resolved RNA 3D structures, there is an urgent need to discover novel motifs with the newly presented information. In this work, we classify all the loops in non-redundant RNA 3D structures to detect plausible RNA structural motif families by using a clustering pipeline...
March 9, 2018: Nucleic Acids Research
Afsaneh Khani, Nicole Popp, Bernd Kreikemeyer, Nadja Patenge
Regulatory RNAs play important roles in the control of bacterial gene expression. In this study, we investigated gene expression regulation by a putative glycine riboswitch located in the 5'-untranslated region of a sodium:alanine symporter family (SAF) protein gene in the group A Streptococcus pyogenes serotype M49 strain 591. Glycine-dependent gene expression mediated by riboswitch activity was studied using a luciferase reporter gene system. Maximal reporter gene expression was observed in the absence of glycine and in the presence of low glycine concentrations...
2018: Frontiers in Microbiology
Chunxia Li, Shiyao Liu, Peiyi Liu, Yaxin Wang, Chunli Xu, Jun Tao, Chaozu He
Riboswitches are RNA elements that sense metabolites and control gene expression. Recently, the yybP-ykoY riboswitches were found to sense manganese (Mn2+) and regulate the expression of diverse genes. Here, we show that the leader RNA (a yybP-ykoY RNA) of yebN in Xanthomonas oryzae pv. oryzae (Xoo) also functions as a sensor of Mn2+. This leader RNA detects Mn2+ levels in plants and is essential to Xoo virulence. Our data also indicate that Mn2+ is not only required as a microelement for plant growth but also acts as a defense molecule to inhibit pathogen growth...
March 9, 2018: Molecular Plant-microbe Interactions: MPMI
Daniel P Morse, Colin E Nevins, Joana Aggrey-Fynn, Rick J Bravo, Herman O I Pfaeffle, Jess E Laney
Riboswitches are RNA elements found in non-coding regions of messenger RNAs that regulate gene expression through a ligand-triggered conformational change. Riboswitches typically bind tightly and specifically to their ligands, so they have the potential to serve as highly effective sensors in vitro. In B. subtilis and other gram-positive bacteria, purine nucleotide synthesis is regulated by riboswitches that bind to guanine. We modified the xpt-pbuX guanine riboswitch for use in a fluorescence quenching assay that allowed us to specifically detect and quantify guanine in vitro...
March 5, 2018: Journal of Biotechnology
Ji Heon Noh, Kyoung Mi Kim, Waverly G McClusky, Kotb Abdelmohsen, Myriam Gorospe
Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides found throughout the cell that lack protein-coding function. Their functions are closely linked to their interaction with RNA-binding proteins (RBPs) and nucleic acids. Nuclear lncRNAs have been studied extensively, revealing complexes with structural and regulatory roles that enable gene organization and control transcription. Cytoplasmic lncRNAs are less well understood, but accumulating evidence indicates that they also form complexes with diverse structural and regulatory functions...
March 8, 2018: Wiley Interdisciplinary Reviews. RNA
Payal Singh, Nilesh Kumar, Minesh Jethva, Saurabh Yadav, Pragati Kumari, Archana Thakur, Hemant Ritturaj Kushwaha
Cyanobacteria are one of the ancient bacterial species occupying a variety of habitats with diverse metabolic preferences. RNA regulators like riboswitches play significant role in controlling the gene expression in prokaryotes. The taxonomic distribution of riboswitches suggests that they might be one of the oldest mechanisms of gene control system. In this paper, we analyzed the distribution of different riboswitch families in various cyanobacterial genomes. It was observed that only four riboswitch classes were abundant in cyanobacteria, B12 -element (Cob)/AdoCbl/AdoCbl-variant riboswitch being the most abundant...
March 2018: Physiology and Molecular Biology of Plants: An International Journal of Functional Plant Biology
Katherine D Launer-Felty, Scott A Strobel
Cyclic dinucleotides are second messenger molecules produced by both prokaryotes and eukaryotes in response to external stimuli. In bacteria, these molecules bind to RNA riboswitches and several protein receptors ultimately leading to phenotypic changes such as biofilm formation, ion transport and secretion of virulence factors. Some cyclic dinucleotide analogs bind differentially to biological receptors and can therefore be used to better understand cyclic dinucleotide mechanisms in vitro and in vivo. However, production of some of these analogs involves lengthy, multistep syntheses...
March 5, 2018: Nucleic Acids Research
Christina Helmling, Dean-Paulos Klötzner, Florian Sochor, Rachel Anne Mooney, Anna Wacker, Robert Landick, Boris Fürtig, Alexander Heckel, Harald Schwalbe
Transcriptional riboswitches modulate downstream gene expression by a tight coupling of ligand-dependent RNA folding kinetics with the rate of transcription. RNA folding pathways leading to functional ON and OFF regulation involve the formation of metastable states within well-defined sequence intervals during transcription. The kinetic requirements for the formation and preservation of these metastable states in the context of transcription remain unresolved. Here, we reversibly trap the previously defined regulatory relevant metastable intermediate of the Mesoplasma florum 2'-deoxyguanosine (2'dG)-sensing riboswitch using a photocaging-ligation approach, and monitor folding to its native state by real-time NMR in both presence and absence of ligand...
March 5, 2018: Nature Communications
Madeline E Sherlock, Narasimhan Sudarsan, Shira Stav, Ronald R Breaker
Gene control systems sometimes interpret multiple signals to set the expression levels of the genes they regulate. In rare instances, ligand-binding riboswitch aptamers form tandem arrangements to approximate the function of specific two-input Boolean logic gates. Here we report the discovery of riboswitch aptamers for phosphoribosyl pyrophosphate (PRPP) that naturally exist either in singlet arrangements, or occur in tandem with guanine aptamers. Tandem guanine-PRPP aptamers can bind the target ligands, either independently or in combination, to approximate the function expected for an IMPLY Boolean logic gate to regulate transcription of messenger RNAs for de novo purine biosynthesis in bacteria...
March 5, 2018: ELife
Xia Zou, Zhenxing Ren, Na Wang, Yin Cheng, Yuanyuan Jiang, Yan Wang, Chenggang Xu
Background: Anaerobic, mesophilic, and cellulolytic Clostridium papyrosolvens produces an efficient cellulolytic extracellular complex named cellulosome that hydrolyzes plant cell wall polysaccharides into simple sugars. Its genome harbors two long cellulosomal clusters: cip - cel operon encoding major cellulosome components (including scaffolding) and xyl - doc gene cluster encoding hemicellulases. Compared with works on cip - cel operon, there are much fewer studies on xyl - doc mainly due to its rare location in cellulolytic clostridia...
2018: Biotechnology for Biofuels
Johnny Truong, Yu-Fang Hsieh, Lynda Truong, Guifang Jia, Ming C Hammond
RNA-based fluorescent (RBF) biosensors have been applied to detect a variety of metabolites in vitro and in live cells. They are designed by combining the ligand sensing domain of natural riboswitches with in vitro selected fluorogenic aptamers. Different biosensor topologies have been developed to accommodate the diversity of riboswitch structures. Here we show that circular permutation of the riboswitch ligand sensing domain also gives functional biosensors, using the SAM-I riboswitch as our model. We reveal that this design can enhance fluorescence turn-on and ligand binding affinity compared to the non-permuted topology...
February 16, 2018: Methods: a Companion to Methods in Enzymology
Siqi Tian, Wipapat Kladwang, Rhiju Das
The structural interconversions that mediate the gene regulatory functions of RNA molecules may be different from classic models of allostery, but the relevant structural correlations have remained elusive in even intensively studied systems. Here, we present a four-dimensional expansion of chemical mapping called lock-mutate-map-rescue (LM 2 R), which integrates multiple layers of mutation with nucleotide-resolution chemical mapping. This technique resolves the core mechanism of the adenine-responsive V. vulnificus add riboswitch, a paradigmatic system for which both Monod-Wyman-Changeux (MWC) conformational selection models and non-MWC alternatives have been proposed...
February 15, 2018: ELife
Rilee Zeinert, Eli Martinez, Jennifer Schmitz, Katherine Senn, Bakhtawar Usman, Vivek Anantharaman, L Aravind, Lauren S Waters
Manganese is an essential trace nutrient for organisms, because of its role in cofactoring enzymes and providing protection against reactive oxygen species (ROS). Many bacteria require manganese to form pathogenic or symbiotic interactions with eukaryotic host cells. However, excess manganese is toxic, requiring cells to have manganese export mechanisms. Bacteria are currently known to possess two widely-distributed classes of manganese export proteins, MntP and MntE, but other types of transporters likely exist...
February 13, 2018: Journal of Biological Chemistry
Marc Vogel, Julia E Weigand, Britta Kluge, Manuel Grez, Beatrix Suess
Splicing is an essential and highly regulated process in mammalian cells. We developed a synthetic riboswitch that efficiently controls alternative splicing of a cassette exon in response to the small molecule ligand tetracycline. The riboswitch was designed to control the accessibility of the 3' splice site by placing the latter inside the closing stem of a conformationally controlled tetracycline aptamer. In the presence of tetracycline, the cassette exon is skipped, whereas it is included in the ligand's absence...
February 6, 2018: Nucleic Acids Research
Samie R Jaffrey
Genetically encoded sensors are important tools for measuring metabolites and other small molecules in vitro and in live cells. Until recently, genetically encoded sensors exclusively comprised fluorescent proteins that undergo changes in Förster resonance energy transfer upon binding a target analyte. However, recently a new class of fluorescent sensor has been developed composed of RNA. These RNA-based sensors rely on Spinach and other RNA mimics of green fluorescent protein. In each case, the RNA-based sensors contain an analyte-binding aptamer domain which transduces binding of the analyte into a conformational change in Spinach...
2018: Advances in Pharmacology
Noreen F Rizvi, John A Howe, Ali Nahvi, Daniel J Klein, Thierry O Fischmann, Hai-Young Kim, Mark A McCoy, Scott S Walker, Alan Hruza, Matthew P Richards, Chad Chamberlin, Peter Saradjian, Margaret T Butko, Gabriel Mercado, Julja Burchard, Corey Strickland, Peter J Dandliker, Graham F Smith, Elliott B Nickbarg
Recent advances in understanding the relevance of non-coding RNA (ncRNA) to disease have increased interest in drugging ncRNA with small molecules. The recent discovery of ribocil, a structurally distinct synthetic mimic of the natural ligand of the flavin mononucleotide (FMN) riboswitch, has revealed the potential chemical diversity of small molecules that target ncRNA. Affinity-selection mass spectrometry (AS-MS) is theoretically applicable to high-throughput screening (HTS) of small molecules binding to ncRNA...
February 7, 2018: ACS Chemical Biology
Dazhi Tan, Stefano Piana, Robert M Dirks, David E Shaw
Molecular dynamics (MD) simulation has become a powerful tool for characterizing at an atomic level of detail the conformational changes undergone by proteins. The application of such simulations to RNA structures, however, has proven more challenging, due in large part to the fact that the physical models ("force fields") available for MD simulations of RNA molecules are substantially less accurate in many respects than those currently available for proteins. Here, we introduce an extensive revision of a widely used RNA force field in which the parameters have been modified, based on quantum mechanical calculations and existing experimental information, to more accurately reflect the fundamental forces that stabilize RNA structures...
January 29, 2018: Proceedings of the National Academy of Sciences of the United States of America
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