DOCSLIB.ORG

Riboswitch Rnas: Using RNA to Sense Cellular Metabolism

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Riboswitch Rnas: Using RNA to Sense Cellular Metabolism Downloaded from genesdev.cshlp.org on February 3, 2014 - Published by Cold Spring Harbor Laboratory Press Riboswitch RNAs: using RNA to sense cellular metabolism Tina M. Henkin Genes Dev. 2008 22: 3383-3390 Access the most recent version at doi:10.1101/gad.1747308 References This article cites 69 articles, 32 of which can be accessed free at: http://genesdev.cshlp.org/content/22/24/3383.full.html#ref-list-1 Email Alerting Receive free email alerts when new articles cite this article - sign up in the box at the top Service right corner of the article or click here. Topic Articles on similar topics can be found in the following collections Collections Bacteria and Viruses (34 articles) Post-transcriptional Control (113 articles) To subscribe to Genes & Development go to: http://genesdev.cshlp.org/subscriptions Copyright © 2008, Cold Spring Harbor Laboratory Press Downloaded from genesdev.cshlp.org on February 3, 2014 - Published by Cold Spring Harbor Laboratory Press REVIEW Riboswitch RNAs: using RNA to sense cellular metabolism Tina M. Henkin1 Department of Microbiology and Center for RNA Biology, The Ohio State University, Columbus, Ohio 43210, USA Riboswitches are RNA elements that undergo a shift in very rapid response to changing environmental condi- structure in response to binding of a regulatory mol- tions. ecule. These elements are encoded within the transcript Gene regulation in bacteria can also use RNA-binding they regulate, and act in cis to control expression of the proteins that interact with the RNA transcript to control coding sequence(s) within that transcript; their function its fate. Regulatory outcomes include effects on attenu- is therefore distinct from that of small regulatory RNAs ation of transcription (in transcriptional units that con- (sRNAs) that act in trans to regulate the activity of other tain a termination signal, designated an attenuator, early RNA transcripts. Riboswitch RNAs control a broad in the transcript), mRNA stability, and translation ini- range of genes in bacterial species, including those in- tiation. Like DNA-binding proteins, RNA-binding pro- volved in metabolism or uptake of amino acids, cofac- teins that function in gene regulation are often expressed tors, nucleotides, and metal ions. Regulation occurs as a constitutively, and their activity is modulated in re- consequence of direct binding of an effector molecule, or sponse to the environmental signal (e.g., Bacillus subti- through sensing of a physical parameter such as tempera- lis TRAP protein is activated by tryptophan). Constitu- ture. Here we review the global role of riboswitch RNAs tive synthesis of a regulatory protein is potentially in bacterial cell metabolism. wasteful of cellular resources, but allows the cell to be poised to respond rapidly to physiological changes. RNA- binding proteins can also regulate their own expression, A wide variety of mechanisms that regulate genes in- via direct binding to their own mRNA (e.g., ribosomal volved in response to environmental changes, including protein autoregulation). availability of cellular metabolites, have been uncovered Recent studies have revealed an important role for in bacteria. Historically, analysis of gene regulation has RNA as a regulatory molecule in bacteria. Small un- focused primarily on DNA-binding regulatory proteins translated regulatory RNAs (sRNAs) can be encoded on that affect the interaction of RNA polymerase (RNAP) the opposite strand of the DNA from their regulatory with the promoter region of the regulated genes. The target (cis-encoded antisense sRNAs) or in other regions DNA-binding proteins may act to increase or decrease of the chromosome (trans-encoded sRNAs) (Wagner et transcription of their target promoters, and the activity al. 2002; Gottesman et al. 2006; Storz et al. 2006; Brantl of the regulatory protein is often modulated by interac- 2007). Both cis- and trans-encoded sRNAs usually act by tion with an effector molecule that activates or represses base-pairing (perfect or imperfect, respectively) with the DNA binding (e.g., lac repressor binding is decreased by target mRNA, often by affecting accessibility of the lactose, trp repressor binding is activated by tryptophan). translation initiation region of the target transcript or by Collaboration of multiple regulatory proteins at a single affecting mRNA stability. Trans-encoded sRNAs can promoter can be used to integrate multiple signals. Use also act by other mechanisms, including titration of a of DNA-binding regulatory proteins requires that the regulatory RNA-binding protein, as in the CsrA system cell encode and express these proteins, often constitu- (Babitzke and Romeo 2007) or direct interaction with tively, so that the proteins are in place to sense the RNAP (Wassarman 2007). Both cis-encoded and trans- physiological signal and promote the appropriate genetic encoded sRNAs can diffuse throughout the cytoplasm to response. Regulation at the level of transcription initia- modulate expression of targets encoded elsewhere in the tion is efficient, however, in that transcript synthesis genome. In systems of this type, the abundance of the occurs only under the appropriate condition. In some sRNA usually changes in response to an environmental cases, regulatory proteins (such as MerR), and even signal, therefore affecting the fate of its mRNA targets. RNAP, may be prebound to the promoter site, allowing a RNA segments can also act to regulate the expression of the transcript in which they are encoded. These RNA [Keywords: RNA structure; gene expression; regulation; transcription at- segments (which are both cis-encoded and cis-acting) can tenuation; translation] serve as targets for RNA-binding proteins or sRNAs, as 1Correspondence. E-MAIL henkin.3@osu.edu. FAX (614) 292-8120. described above, or can directly monitor a regulatory sig- Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1747308. nal without the assistance of any additional regulatory GENES & DEVELOPMENT 22:3383–3390 © 2008 by Cold Spring Harbor Laboratory Press ISSN 0890-9369/08; www.genesdev.org 3383 Downloaded from genesdev.cshlp.org on February 3, 2014 - Published by Cold Spring Harbor Laboratory Press Henkin factor. Regardless of the involvement of a separate regu- latory factor that transmits the signal to the regulatory element in the transcript, changes in the structure of the target RNA can affect gene expression. This effect is most commonly mediated through controlling the for- mation of the helix of an intrinsic transcription termi- nator (which therefore determines whether transcription terminates early) or through controlling formation of a helix that sequesters the translation initiation region of the downstream transcript (Grundy and Henkin 2006). Effects on mRNA stability can also occur, either through direct modulation of cleavage by specific ribonucleases or by secondary outcomes of primary effects on transla- tional efficiency (as nontranslated mRNAs are often more susceptible to degradation). RNAs that directly monitor a physiological signal, in the absence of any other cellular factor (such as a regulatory protein or Figure 2. Basic model of a standard metabolite-binding ribo- translating ribosome), and exhibit structural shifts in re- switch RNA. (Left) In the absence of the effector, the ligand- sponse to that signal have been termed riboswitches. binding domain (L) is unoccupied, and the RNA is in a confor- These RNAs fall into several different groups that differ mation that allows expression of the downstream coding se- in their overall architecture and the type of signal they quence, either through formation of an antiterminator element (AT) that prevents formation of the terminator helix and there- recognize. The recognized signals include various small fore allows transcription to continue (top), or through capture of molecules (e.g., cofactors, amino acids, nucleotides, and the ASD into a structure that liberates the SD sequence and metal ions), cellular components (e.g., specific tRNAs), allows translation to initiate (bottom). (Right) In the presence of and temperature. Overall, riboswitch RNAs can have a the effector (*), the ligand-binding domain is occupied, resulting major impact on cell physiology because of the large in a structural shift in the downstream region of the RNA. This number of gene families that they regulate. allows the terminator (T) to form, which results in premature termination of transcription (top) or sequestration of the SD sequence in an ASD–SD helix that prevents translation initia- Riboswitch architecture tion (bottom). Variations from this basic model are discussed in the text. Several classes of riboswitch RNA structural arrange- ments have emerged. The simplest class of riboswitches instead tuned to the melting temperature of the inhibi- are the RNA thermosensors. These are RNA structural tory helix. Small changes in the stability of the helix can elements that affect expression of the downstream therefore result in major changes in gene expression and genes, usually by sequestration of the Shine-Dalgarno in temperature response. These regulatory elements are (SD) sequence (Narberhaus et al. 2006). The regulatory often used to control genes that allow the cell to respond response occurs in response to a change in temperature to sudden changes in temperature, including heat-shock rather than binding of an effector molecule. In most genes (Morita et al. 1999); this type of system is also used cases, the RNA is in an inactive state (e.g., with the SD in pathogenic organisms to induce virulence gene ex- inaccessible to ribosome binding) under normal growth pression in response to entry of the bacterium into a conditions, but an increase in temperature results in the mammalian host (Johansson et al. 2002). melting of the RNA helix and release of the SD sequence In contrast to the single-domain thermosensor RNAs, into a single-stranded state (Fig. 1). RNA thermosensors a standard small molecule-binding riboswitch RNA is differ from other riboswitches in that no effector recog- comprised of two separate elements, a ligand-binding do- nition domain is required, with the regulatory response main and a gene expression domain (Fig.
Load more

Recommended publications
  • Exploring the Structure of Long Non-Coding Rnas, J
    IMF YJMBI-63988; No. of pages: 15; 4C: 3, 4, 7, 8, 10 1 2 Rise of the RNA Machines: Exploring the Structure of 3 Long Non-Coding RNAs 4 Irina V. Novikova, Scott P. Hennelly, Chang-Shung Tung and Karissa Y. Sanbonmatsu Q15 6 Los Alamos National Laboratory, Los Alamos, NM 87545, USA 7 Correspondence to Karissa Y. Sanbonmatsu: kys@lanl.gov 8 http://dx.doi.org/10.1016/j.jmb.2013.02.030 9 Edited by A. Pyle 1011 12 Abstract 13 Novel, profound and unexpected roles of long non-coding RNAs (lncRNAs) are emerging in critical aspects of 14 gene regulation. Thousands of lncRNAs have been recently discovered in a wide range of mammalian 15 systems, related to development, epigenetics, cancer, brain function and hereditary disease. The structural 16 biology of these lncRNAs presents a brave new RNA world, which may contain a diverse zoo of new 17 architectures and mechanisms. While structural studies of lncRNAs are in their infancy, we describe existing 18 structural data for lncRNAs, as well as crystallographic studies of other RNA machines and their implications 19 for lncRNAs. We also discuss the importance of dynamics in RNA machine mechanism. Determining 20 commonalities between lncRNA systems will help elucidate the evolution and mechanistic role of lncRNAs in 21 disease, creating a structural framework necessary to pursue lncRNA-based therapeutics. 22 © 2013 Published by Elsevier Ltd. 24 23 25 Introduction rather than the exception in the case of eukaryotic 50 organisms. 51 26 RNA is primarily known as an intermediary in gene LncRNAs are defined by the following: (i) lack of 52 11 27 expression between DNA and proteins.
    [Show full text]
  • RNA Regulatory Elements Play a Significant Role in Gene
    Ab initio IDENTIFICATION OF REGULATORY RNAS USING INFORMATION-THEORETIC UNCERTAINTY by AMIRHOSSEIN MANZOUROLAJDAD (Under the Direction of Dr. Jonathan Arnold) ABSTRACT RNA regulatory elements play a significant role in gene regulation. Riboswitches are regulatory elements which function by forming a ligand-induced alternative fold that controls access to ribosome binding sites or other regulatory sites in RNA. Traditionally, riboswitches have been identified based on sequence and structural homology. In this work, in an attempt to devise an ab initio method for identification of regulatory elements, mainly riboswitches, we derive and implement Shannon’s entropy of the SCFG ensemble on an RNA sequence in polynomial time for both structurally ambiguous and unambiguous grammars. We then evaluate the significance of this new measure of structural entropy in identifying riboswitches. Finally, sim- ple lightweight stochastic context-free grammar folding models assign significant values to long extensive secondary structures in Bacillus subtilis. INDEX WORDS: Riboswitch, RNA Secondary Structure, Stochastic Context-free Grammars, Information Theory Ab initio IDENTIFICATION OF REGULATORY RNAS USING INFORMATION-THEORETIC UNCERTAINTY by AMIRHOSSEIN MANZOUROLAJDAD BS, The University of Guilan, Rasht, Iran, 2004 MS, Isfahan University of Technology, Isfahan, Iran, 2007 A Dissertation Submitted to the Graduate Faculty of The University of Georgia in Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY ATHENS,GEORGIA 2014 ⃝c 2014 Amirhossein Manzourolajdad All Rights Reserved Ab initio IDENTIFICATION OF REGULATORY RNAS USING INFORMATION-THEORETIC UNCERTAINTY by AMIRHOSSEIN MANZOUROLAJDAD Approved: Major Professor: Jonathan Arnold Committee: Sidney Kushner Russell L. Malmberg Jan Mrazek Electronic Version Approved: Maureen Grasso Dean of the Graduate School The University of Georgia May 2014 I dedicate this work to my mother, Roya iv ACKNOWLEGEMENTS I will be eternally indebted to my major advisor Dr.
    [Show full text]
  • Characterization of the Smk Box: a Riboswitch
    CHARACTERIZATION OF THE SMK BOX: A RIBOSWITCH THAT BINDS S-ADENOSYLMETHIONINE DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Ryan T. Fuchs, B.S. Graduate Program in Microbiology The Ohio State University 2009 Dissertation Committee: Professor Tina M. Henkin, Adviser Professor Juan D. Alfonzo Professor Charles J. Daniels Professor Kurt Fredrick ABSTRACT Riboswitches are conserved RNA sequences that regulate downstream gene expression via changes in the RNA structure. Riboswitches usually respond to an environmental stimulus, typically binding of an effector molecule, that causes a structural rearrangement without additional trans-acting factors. The structural rearrangement can cause or prevent the formation of an intrinsic transcriptional terminator to regulate the gene at the level of premature transcription termination, or it can modulate the accessibility of the ribosome binding site to regulate at the level of translation initiation. Previous work has shown that there are multiple classes of riboswitches that bind S- adenosylmethionine (SAM) and regulate genes involved in biosynthesis of methionine, cysteine and SAM. The S box (or SAM-I) riboswitches are found in a wide range of bacteria while the SAM-II riboswitch is found primarily in Proteobacteria. Both riboswitches recognize SAM in a similar manner, but they are very different in terms of sequence, secondary and tertiary structure. This demonstrates that it is possible for bacteria to evolve very different regulatory RNAs to respond to the same metabolite. We discovered a third SAM binding riboswitch motif (called the SMK box or SAM-III) upstream of the metK gene (encoding SAM synthetase) in many Lactobacillales species.
    [Show full text]
  • Secondary Structural Entropy in RNA Switch (Riboswitch) Identification Amirhossein Manzourolajdad1,2* and Jonathan Arnold1,3
    Manzourolajdad and Arnold BMC Bioinformatics (2015) 16:133 DOI 10.1186/s12859-015-0523-2 METHODOLOGY ARTICLE Open Access Secondary structural entropy in RNA switch (Riboswitch) identification Amirhossein Manzourolajdad1,2* and Jonathan Arnold1,3 *Correspondence: amanzour@uga.edu Abstract 1 Institute of Bioinformatics, Background: RNA regulatory elements play a significant role in gene regulation. University of Georgia, Davison Life Sciences Bldg, Room B118B, 120 Riboswitches, a widespread group of regulatory RNAs, are vital components of many Green St, 30602 Athens, USA bacterial genomes. These regulatory elements generally function by forming a 2 National Center for Biotechnology ligand-induced alternative fold that controls access to ribosome binding sites or other Information (NCBI), NIH, Building 38A, RM 6S614K, 8600 Rockville regulatory sites in RNA. Riboswitch-mediated mechanisms are ubiquitous across Pike, 20894 Bethesda, USA bacterial genomes. A typical class of riboswitch has its own unique structural and Full list of author information is available at the end of the article biological complexity, making de novo riboswitch identification a formidable task. Traditionally, riboswitches have been identified through comparative genomics based on sequence and structural homology. The limitations of structural-homology-based approaches, coupled with the assumption that there is a great diversity of undiscovered riboswitches, suggests the need for alternative methods for riboswitch identification, possibly based on features intrinsic to their structure. As of yet, no such reliable method has been proposed. Results: We used structural entropy of riboswitch sequences as a measure of their secondary structural dynamics. Entropy values of a diverse set of riboswitches were compared to that of their mutants, their dinucleotide shuffles, and their reverse complement sequences under different stochastic context-free grammar folding models.
    [Show full text]
  • Developing a Riboswitch-Mediated Regulatory System for Metabolic Flux Control in Thermophilic Bacillus Methanolicus
    International Journal of Molecular Sciences Article Developing a Riboswitch-Mediated Regulatory System for Metabolic Flux Control in Thermophilic Bacillus methanolicus Marta Irla , Sigrid Hakvåg and Trygve Brautaset * Department of Biotechnology and Food Sciences, Norwegian University of Science and Technology, 7034 Trondheim, Norway; marta.k.irla@ntnu.no (M.I.); sigrid.hakvaag@sintef.no (S.H.) * Correspondence: trygve.brautaset@ntnu.no; Tel.: +47-73593315 Abstract: Genome-wide transcriptomic data obtained in RNA-seq experiments can serve as a re- liable source for identification of novel regulatory elements such as riboswitches and promoters. Riboswitches are parts of the 50 untranslated region of mRNA molecules that can specifically bind various metabolites and control gene expression. For that reason, they have become an attractive tool for engineering biological systems, especially for the regulation of metabolic fluxes in industrial microorganisms. Promoters in the genomes of prokaryotes are located upstream of transcription start sites and their sequences are easily identifiable based on the primary transcriptome data. Bacillus methanolicus MGA3 is a candidate for use as an industrial workhorse in methanol-based biopro- cesses and its metabolism has been studied in systems biology approaches in recent years, including transcriptome characterization through RNA-seq. Here, we identify a putative lysine riboswitch in B. methanolicus, and test and characterize it. We also select and experimentally verify 10 putative B. methanolicus-derived promoters differing in their predicted strength and present their functionality in combination with the lysine riboswitch. We further explore the potential of a B. subtilis-derived purine riboswitch for regulation of gene expression in the thermophilic B. methanolicus, establishing a Citation: Irla, M.; Hakvåg, S.; novel tool for inducible gene expression in this bacterium.
    [Show full text]
  • Structural and Mechanistic Studies of the THI Box and SMK Box Riboswitches
    Structural and Mechanistic Studies of the THI Box and SMK Box Riboswitches Dissertation Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Angela Mae Smith, M.S. Graduate Program in Microbiology The Ohio State University 2009 Dissertation Committee: Professor Tina Henkin, Advisor Professor Kurt Fredrick Professor Michael Ibba Professor Ross Dalbey ABSTRACT Organisms have evolved a variety of mechanisms for regulating gene expression. Expression of individual genes is carefully modulated during different stages of cell development and in response to changing environmental conditions. A number of regulatory mechanisms involve structural elements within messenger RNAs (mRNAs) that, in response to an environmental signal, undergo a conformational change that affects expression of a gene encoded on that mRNA. RNA elements of this type that operate independently of proteins or translating ribosomes are termed riboswitches. In this work, the THI box and SMK box riboswitches were investigated in order to gain insight into the structural basis for ligand recognition and the mechanism of regulation employed by each of these RNAs. Both riboswitches are predicted to regulate at the level of translation initiation using a mechanism in which the Shine-Dalgarno (SD) sequence is occluded in response to ligand binding. For the THI box riboswitch, the studies presented here demonstrated that 30S ribosomal subunit binding at the SD region decreases in the presence of thiamin pyrophosphate (TPP). Mutation of conserved residues in the ligand binding domain resulted in loss of TPP-dependent repression in vivo. Based on these experiments two classes of mutant phenotypes were identified.
    [Show full text]
  • A Mechanism for Ligand Gated Strand Displacement in ZTP Riboswitch Transcription Regulation
    bioRxiv preprint doi: https://doi.org/10.1101/521930; this version posted January 16, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. A mechanism for ligand gated strand displacement in ZTP riboswitch transcription regulation Eric J. Strobel1*, Luyi Cheng2,4, Katherine E. Berman2,4, Paul D. Carlson3,4, Julius B. Lucks1,4* Affiliations: 1Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA 2Interdisciplinary Biological Sciences Graduate Program, Northwestern University, Evanston, IL 60208, USA 3Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, 14853, USA 4Center for Synthetic Biology, Northwestern University, Evanston, IL, 20208 *Correspondence to: Email: eric.strobel@northwestern.edu, jblucks@northwestern.edu Abstract Cotranscriptional RNA folding forms structural intermediates that can be critically important for RNA biogenesis. This is especially true for transcriptional riboswitches that must undergo ligand-dependent structural changes during transcription to regulate the synthesis of downstream genes. Here, we systematically map the folding states traversed by the Clostridium beijerinckii pfl riboswitch as it controls transcription termination in response to the purine biosynthetic intermediate ZMP. We find that after rearrangement of a non-native hairpin to form the ZTP aptamer, cotranscriptional ZMP binding stabilizes two structural elements that lead to antitermination by tuning the efficiency of terminator hairpin nucleation and strand displacement. We also uncover biases within natural ZTP riboswitch sequences that could avoid misfolded intermediates that disrupt function.
    [Show full text]
  • Structure and Ligand Binding of the Glutamine-II Riboswitch
    Nucleic Acids Research, 2019 1 doi: 10.1093/nar/gkz539 Structure and ligand binding of the glutamine-II riboswitch 1, 1, 2 2 1,* Lin Huang †,JiaWang †,AndrewM.Watkins , Rhiju Das and David M. J. Lilley 1 Cancer Research UK Nucleic Acid Structure Research Group, MSI/WTB Complex, The University of Dundee, Dow June 2019 26 on by guest https://academic.oup.com/nar/advance-article-abstract/doi/10.1093/nar/gkz539/5520577 from Downloaded Street, Dundee DD1 5EH, UK and 2Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA Received March 25, 2019; Revised May 31, 2019; Editorial Decision June 03, 2019; Accepted June 06, 2019 ABSTRACT GS-inactivating protein factors IF7 and IF17, encoded by gifA and gifB, respectively (7,8). Ames and Breaker (9) iden- We have determined the structure of the glutamine-II tifed two 60 nt elements in the 5′-UTRs of genes involved riboswitch ligand binding domain using X-ray crys- in nitrogen∼ metabolism in cyanobacterial and metagenomic tallography. The structure was solved using a novel sequences. One is based on a three-way helical junction with combination of homology modeling and molecular a loop E motif, termed glnA, and the other with a pseu- replacement. The structure comprises three coaxial doknot termed the downstream peptide (DP) motif. Us- helical domains, the central one of which is a pseudo- ing in-line probing they demonstrated that the RNA binds knot with partial triplex character. The major groove L-glutamine with mM affnity, but discriminated against a of this helix provides the binding site for L-glutamine, series of similar compounds.
    [Show full text]
  • Riboswitch-Dependent Gene Regulation and Its Evolution in the Plant Kingdom
    Downloaded from genesdev.cshlp.org on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press RESEARCH COMMUNICATION related compounds (Sudarsan et al. 2005). In prokaryotes, Riboswitch-dependent gene genetic control mediated by riboswitches is a prevalent regulation and its evolution phenomenon, and the dozen riboswitches identified to date regulate >3% of all bacterial genes (Nudler 2006). in the plant kingdom Thiamin pyrophosphate (TPP) is a coenzyme derived from vitamin B1 (thiamin) that is synthesized by bacte- 1,2 1 1 Samuel Bocobza, Avital Adato, Tali Mandel, ria, fungi, and plants, and serves as a dietary requirement Michal Shapira,2 Evgeny Nudler,3 and for humans and other animals. It is an obligatory cofac- Asaph Aharoni1,4 tor that plays an important role in amino acid and car- bohydrate metabolism; thus, fine control of its levels is 1Department of Plant Sciences, Weizmann Institute of essential for the viability of all living cells. TPP-binding Science, Rehovot 76100, Israel; 2Department of Life Sciences, riboswitches, first identified in Bacillus subtilis and Ben Gurion University, Beer Sheva 84105, Israel; 3Department Escherichia coli (Mironov et al. 2002; Winkler et al. of Biochemistry, New York University School of Medicine, 2002), exist in the genomes of species belonging to most New York, New York 10016, USA bacterial phyla (Rodionov et al. 2002). Binding of TPP by the riboswitch down-regulates expression of thiamin Riboswitches are natural RNA sensors that affect gene biosynthesis genes by inducing either the formation of a control via their capacity to bind small molecules. Their transcription terminator hairpin or the formation of a prevalence in higher eukaryotes is unclear.
    [Show full text]
  • Bioinformatic Analysis of Riboswitch Structures Uncovers Variant Classes
    Bioinformatic analysis of riboswitch structures PNAS PLUS uncovers variant classes with altered ligand specificity Zasha Weinberga,1,2, James W. Nelsonb,1,3, Christina E. Lünseb,4, Madeline E. Sherlockc, and Ronald R. Breakera,b,c,5 aHoward Hughes Medical Institute, Yale University, New Haven, CT 06520; bDepartment of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520; and cDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520 Contributed by Ronald R. Breaker, February 2, 2017 (sent for review December 8, 2016; reviewed by Robert T. Batey and Elena Rivas) Riboswitches are RNAs that form complex, folded structures that Several variant riboswitches share a number of characteristics selectively bind small molecules or ions. As with certain groups of that could have been exploited in a bioinformatic search for such protein enzymes and receptors, some riboswitch classes have RNAs. We chose to apply three important properties common to evolved to change their ligand specificity. We developed a pro- the guanine/adenine (15) and c-di-GMP-I/c-AMP-GMP (13, 14) cedure to systematically analyze known riboswitch classes to find riboswitch sets, among other variants. The first of these proper- additional variants that have altered their ligand specificity. This ties is that some variant riboswitches with altered ligand speci- approach uses multiple-sequence alignments, atomic-resolution ficity will remain somewhat close in both sequence and structure structural information, and riboswitch gene associations. Among to the predominant or “parent” class. For example, the initial the discoveries are unique variants of the guanine riboswitch class collections of representatives for guanine (23) and c-di-GMP-I ′ that most tightly bind the nucleoside 2 -deoxyguanosine.
    [Show full text]
  • The RNA World New Discoveries Reflecting Ancient Biology
    The RNA World New Discoveries Reflecting Ancient Biology Ronald R. Breaker Yale University Howard Hughes Medical Institute 5 March 2014; CAPS Tree of Life RNA World You are here 2 Why RNA? Biological Information RNA Replication and Transfer 3 Origins of the RNA World Theory Carl Woese (1967) The Genetic Code, Harper and Row Leslie Orgel (1968) Evolution of the Genetic Apparatus J. Mol. Biol. 38:381 Francis Crick (1968) The Origin of the Genetic Code J. Mol. Biol. 38:367 4 ● DNA monomers are made from RNA monomers. ● Most coenzymes are derivatives of RNA. ● Information transfer from DNA to proteins intimately involves RNA. ● RNA-based sensors and switches exist (riboswitches). ● RNA naturally stores genetic information and catalyzes chemical reactions (ribozymes). ● All encoded proteins are made by ribozymes. ● Ancient structured noncoding RNAs could have allowed RNA World organisms to run a complex metabolic state. ● Many structured noncoding RNAs might exist in modern cells and are awaiting discovery. Riboswitches Natural RNA Elements that Bind Metabolites and Control Gene Expression The Typical Architecture of Riboswitches in Bacteria TPP Riboswitches Present in All Three Domains of Life McCown, P.J., Breaker, R.R., unpublished The Moving Parts of Riboswitches Aptamers and Expression Platforms The two most common mechanisms of riboswitch gene control in eubacteria. Transcription Control Translation Control A stealth form of transcription control? The Diversity and Distribution of Riboswitches Data derived from the analysis of ~10,000
    [Show full text]
  • Core Requirements of the Adenine Riboswitch Aptamer for Ligand Binding
    JOBNAME: RNA 13#3 2007 PAGE: 1 OUTPUT: Wednesday February 7 07:09:20 2007 csh/RNA/131630/rna1420 Downloaded from rnajournal.cshlp.org on September 29, 2021 - Published by Cold Spring Harbor Laboratory Press Core requirements of the adenine riboswitch aptamer for ligand binding JEAN-FRANCxOIS LEMAY and DANIEL A. LAFONTAINE De´partement de biologie, Faculte´ des sciences, Universite´ de Sherbrooke, Que´bec, J1K 2R1, Canada ABSTRACT The adenine riboswitch aptamer, the A box, positively regulates gene expression upon adenine binding. To provide insight into structure–function relationships, important for the adenine riboswitch aptamer, we have created alignments for six aptamer sequences that reveal the core requirements. In addition, 2-aminopurine (2AP) binding studies have been used to test the consensus sequence derived from the alignment. Overall, the consensus secondary structure is consistent with 2AP binding studies. However, a position in the core, previously identified as variable, shows restriction in nucleotide sequence. Further- more, this restriction is found to be related with the ligand specificity of the riboswitch. The implications of this relationship for the riboswitch gene regulation mechanism are discussed. Keywords: riboswitch; RNA structure; RNA folding; aptamer; molecular recognition; fluorescence spectroscopy INTRODUCTION 2003), glucosamine-6-phosphate (Winkler et al. 2004), glycine (Mandal et al. 2004), lysine (Grundy et al. 2003; Riboswitches are regulatory elements found predominantly Sudarsan et al. 2003b), intracellular magnesium (Cromie in 59-untranslated regions of messenger RNAs (mRNAs). et al. 2006), S-adenosylmethionine (Epshtein et al. 2003; These genetic switches are highly structured domains that McDaniel et al. 2003; Winkler et al. 2003), and thiamine can bind cellular metabolites and regulate the expression of pyrophosphate (Mironov et al.
    [Show full text]