Skip to main content

Beyond Crystallography: Investigating the Conformational Dynamics of the Purine Riboswitch

  • Chapter
Non-Protein Coding RNAs

Part of the book series: Springer Series in Biophysics ((BIOPHYSICS,volume 13))

Riboswitches are structured elements located in the 5′-untranslated regions of numerous bacterial mRNAs that serve to regulate gene expression via their ability to specifically bind metabolites. The purine riboswitch ligand-binding domain has emerged as an important model system for investigating the relationship between RNA structure and function. Directed by NMR and crystallographically generated structures of this RNA, a variety of biophysical and biochemical techniques have been utilized to understand its dynamic nature. In this review, we describe these various approaches and what they reveal about the purine riboswitch.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Abbreviations

2AP:

2-aminopurine

FRET:

fluorescence resonance energy transfer

J:

joining region

L:

loop

NMIA:

N-methylisatoic anhydride

SHAPE:

selective 2′-hydroxyl acylation analyzed by primer extension

smFRET:

single molecule fluorescence resonance energy transfer

TPP:

thiamine pyrophosphate

UTR:

untranslated region

References

  • Barrick JE, Corbino KA, Winkler WC, Nahvi A, Mandal M, Collins J, Lee M, Roth A, Sudarsan N, Jona I, Wickiser JK, Breaker RR (2004) New RNA motifs suggest an expanded scope for riboswitches in bacterial genetic control. Proc Natl Acad Sci U S A 101:6421–6426

    Article  ADS  Google Scholar 

  • Batey RT, Gilbert SD, Montange RK (2004) Structure of a natural guanine-responsive riboswitch complexed with the metabolite hypoxanthine. Nature 432:411–415

    Article  ADS  Google Scholar 

  • Blouin S, Lafontaine DA (2007) A loop–loop interaction and a K-turn motif located in the lysine aptamer domain are important for the riboswitch gene regulation control. RNA 13:1256–1267

    Article  Google Scholar 

  • Buck J, Furtig B, Noeske J, Wohnert J, Schwalbe H (2007) Time-resolved NMR methods resolving ligand-induced RNA folding at atomic resolution. Proc Natl Acad Sci U S A 104:15699–15704

    Article  ADS  Google Scholar 

  • Cheah MT, Wachter A, Sudarsan N, Breaker RR (2007) Control of alternative RNA splicing and gene expression by eukaryotic riboswitches. Nature 447:497–500

    Article  ADS  Google Scholar 

  • Cromie MJ, Shi Y, Latifi T, Groisman EA (2006) An RNA sensor for intracellular Mg(2+). Cell 125:71–84

    Article  Google Scholar 

  • Da Costa CP, Fedor MJ, Scott LG (2007) 8-Azaguanine reporter of purine ionization states in structured RNAs. J Am Chem Soc 129:3426–3432

    Article  Google Scholar 

  • Dann CE III, Wakeman CA, Sieling CL, Baker SC, Irnov I, Winkler WC (2007) Structure and mechanism of a metal-sensing regulatory RNA. Cell 130:878–892

    Article  Google Scholar 

  • Ehresmann C, Baudin F, Mougel M, Romby P, Ebel JP, Ehresmann B (1987) Probing the structure of RNAs in solution. Nucleic Acids Res 15:9109–9128

    Article  Google Scholar 

  • Eskandari S, Prychyna O, Leung J, Avdic D, O'Neill MA (2007) Ligand-directed dynamics of adenine riboswitch conformers. J Am Chem Soc 129:11308–11309

    Article  Google Scholar 

  • Gilbert SD, Batey RT (2005) Riboswitches: natural selexion. Cell Mol Life Sci 62:2401–2404

    Article  Google Scholar 

  • Gilbert SD, Stoddard CD, Wise SJ, Batey RT (2006) Thermodynamic and kinetic characterization of ligand binding to the purine riboswitch aptamer domain. J Mol Biol 359:754–768

    Article  Google Scholar 

  • Griffiths-Jones S, Moxon S, Marshall M, Khanna A, Eddy SR, Bateman A (2005) Rfam: annotating non-coding RNAs in complete genomes. Nucleic Acids Res 33:D121–D124

    Article  Google Scholar 

  • Grundy FJ, Henkin TM (1998) The S box regulon: a new global transcription termination control system for methionine and cysteine biosynthesis genes in gram-positive bacteria. Mol Microbiol 30:737–749

    Article  Google Scholar 

  • Irnov A, Winkler WC (2006) Genetic control by cis-acting regulatory RNAs in Bacillus subtilis: general principles and propects for discovery. Cold Spring Harb Symp Quant Biol 71: 239–249

    Article  Google Scholar 

  • Jucker FM, Phillips RM, McCallum SA, Pardi A (2003) Role of a heterogeneous free state in the formation of a specific RNA-theophylline complex. Biochemistry 42:2560–2567

    Article  Google Scholar 

  • Lemay JF, Penedo JC, Tremblay R, Lilley DMJ, Lafontaine DA (2006) Folding of the adenine riboswitch. Chem Biol 13:857–868

    Article  Google Scholar 

  • Leulliot N, Varani G (2001) Current topics in RNA-protein recognition: control of specificity and biological function through induced fit and conformational capture. Biochemistry 40: 7947–7956

    Article  Google Scholar 

  • Mandal M, Breaker RR (2004) Adenine riboswitches and gene activation by disruption of a transcription terminator. Nat Struct Mol Biol 11:29–35

    Article  Google Scholar 

  • Mandal M, Boese B, Barrick JE, Winkler WC, Breaker RR (2003) Riboswitches control fundamental biochemical pathways in Bacillus subtilis and other bacteria. Cell 113:577–586

    Article  Google Scholar 

  • Mandal M, Lee M, Barrick JE, Weinberg Z, Emilsson GM, Ruzzo WL, Breaker RR (2004) A glycine-dependent riboswitch that uses cooperative binding to control gene expression. Science 306:275–279

    Article  ADS  Google Scholar 

  • McDaniel BA, Grundy FJ, Henkin TM (2005) A tertiary structural element in S box leader RNAs is required for S-adenosylmethionine-directed transcription termination. Mol Microbiol 57:1008–1021

    Article  Google Scholar 

  • Miranda-Rios J, Navarro M, Soberon M (2001) A conserved RNA structure (thi box) is involved in regulation of thiamin biosynthetic gene expression in bacteria. Proc Natl Acad Sci U S A 98:9736–9741

    Article  ADS  Google Scholar 

  • Mironov AS, Gusarov I, Rafikov R, Lopez LE, Shatalin K, Kreneva RA, Perumov DA, Nudler E (2002) Sensing small molecules by nascent RNA: a mechanism to control transcription in bacteria. Cell 111:747–756

    Article  Google Scholar 

  • Mortimer SA, Weeks KM (2007) A fast-acting reagent for accurate analysis of RNA secondary and tertiary structure by SHAPE chemistry. J Am Chem Soc 129:4144–4145

    Article  Google Scholar 

  • Nahvi A, Sudarsan N, Ebert MS, Zou X, Brown KL, Breaker RR (2002) Genetic control by a metabolite binding mRNA. Chem Biol 9:1043

    Article  Google Scholar 

  • Noeske J, Richter C, Grundl MA, Nasiri HR, Schwalbe H, Wohnert J (2005) An intermolecular base triple as the basis of ligand specificity and affinity in the guanine- and adenine-sensing riboswitch RNAs. Proc Natl Acad Sci U S A 102:1372–1377

    Article  ADS  Google Scholar 

  • Noeske J, Buck J, Furtig B, Nasiri HR, Schwalbe H, Wohnert J (2007a) Interplay of ‘induced fit’ and preorganization in the ligand induced folding of the aptamer domain of the guanine binding riboswitch. Nucleic Acids Res 35:572–583

    Article  Google Scholar 

  • Noeske J, Schwalbe H, Wohnert J (2007b) Metal-ion binding and metal-ion induced folding of the adenine-sensing riboswitch aptamer domain. Nucleic Acids Res 35:5262–5273

    Article  Google Scholar 

  • Ottink OM, Rampersad SM, Tessari M, Zaman GJ, Heus HA, Wijmenga SS (2007) Ligand-induced folding of the guanine-sensing riboswitch is controlled by a combined predetermined induced fit mechanism. RNA 13:2202–2212

    Article  Google Scholar 

  • Rieder R, Lang K, Graber D, Micura R (2007) Ligand-induced folding of the adenosine deaminase A-riboswitch and implications on riboswitch translational control. Chembiochem 8:896–902

    Article  Google Scholar 

  • Rodionov DA, Vitreschak AG, Mironov AA, Gelfand MS (2003) Regulation of lysine biosynthesis and transport genes in bacteria: yet another RNA riboswitch? Nucleic Acids Res 31: 6748–6757

    Article  Google Scholar 

  • Serganov A, Yuan YR, Pikovskaya O, Polonskaia A, Malinina L, Phan AT, Hobartner C, Micura R, Breaker RR, Patel DJ (2004) Structural basis for discriminative regulation of gene expression by adenine- and guanine-sensing mRNAs. Chem Biol 11:1729–1741

    Article  Google Scholar 

  • Stoddard CD, Batey RT (2006) Mix-and-match riboswitches. ACS Chem Biol 1:751–754

    Article  Google Scholar 

  • Stoddard CD, Gilbert SD, Batey RT (2008) Ligand-dependent folding of the three-way junction in the purine riboswitch. RNA 14:675–668

    Article  Google Scholar 

  • Sudarsan N, Barrick JE, Breaker RR (2003a) Metabolite-binding RNA domains are present in the genes of eukaryotes. RNA 9:644–647

    Article  Google Scholar 

  • Sudarsan N, Wickiser JK, Nakamura S, Ebert MS, Breaker RR (2003b) An mRNA structure in bacteria that controls gene expression by binding lysine. Genes Dev 17:2688–2697

    Article  Google Scholar 

  • Wachter A, Tunc-Ozdemir M, Grove BC, Green PJ, Shintani DK, Breaker RR (2007) Riboswitch control of gene expression in plants by splicing and alternative 3′ end processing of mRNAs. Plant Cell 19(11):3437–3450

    Article  Google Scholar 

  • Walter NG, Harris DA, Pereira MJ, Rueda D (2001) In the fluorescent spotlight: global and local conformational changes of small catalytic RNAs. Biopolymers 61:224–242

    Article  Google Scholar 

  • Weinberg Z, Barrick JE, Yao Z, Roth A, Kim JN, Gore J, Wang JX, Lee ER, Block KF, Sudarsan N, Neph S, Tompa M, Ruzzo WL, Breaker RR (2007) Identification of 22 candidate structured RNAs in bacteria using the CMfinder comparative genomics pipeline. Nucleic Acids Res 35:4809–4819

    Article  Google Scholar 

  • Wickiser JK, Cheah MT, Breaker RR, Crothers DM (2005a) The kinetics of ligand binding by an adenine-sensing riboswitch. Biochemistry 44:13404–13414

    Article  Google Scholar 

  • Wickiser JK, Winkler WC, Breaker RR, Crothers DM (2005b) The speed of RNA transcription and metabolite binding kinetics operate an FMN riboswitch. Mol Cell 18:49–60

    Article  Google Scholar 

  • Wilkinson KA, Merino EJ, Weeks KM (2005) RNA SHAPE chemistry reveals nonhierarchical interactions dominate equilibrium structural transitions in tRNA(Asp) transcripts. J Am Chem Soc 127:4659–4667

    Article  Google Scholar 

  • Wilkinson KA, Merino EJ, Weeks KM (2006) Selective 2′-hydroxyl acylation analyzed by primer extension (SHAPE): quantitative RNA structure analysis at single nucleotide resolution. Nat Protoc 1:1610–1616

    Article  Google Scholar 

  • Williamson JR (2000) Induced fit in RNA-protein recognition. Nat Struct Biol 7:834–837

    Article  Google Scholar 

  • Winkler WC, Breaker RR (2005) Regulation of bacterial gene expression by riboswitches. Annu Rev Microbiol 59:487–517

    Article  Google Scholar 

  • Winkler WC, Grundy FJ, Murphy BA, Henkin TM (2001) The GA motif: an RNA element common to bacterial antitermination systems, rRNA, and eukaryotic RNAs. RNA 7:1165–1172

    Article  Google Scholar 

  • Winkler WC, Cohen-Chalamish S, Breaker RR (2002) An mRNA structure that controls gene expression by binding FMN. Proc Natl Acad Sci U S A 99:15908–15913

    Article  ADS  Google Scholar 

  • Winkler WC, Nahvi A, Roth A, Collins JA, Breaker RR (2004) Control of gene expression by a natural metabolite-responsive ribozyme. Nature 428:281–286

    Article  ADS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Stoddard, C.D., Batey, R.T. (2009). Beyond Crystallography: Investigating the Conformational Dynamics of the Purine Riboswitch. In: Walter, N.G., Woodson, S.A., Batey, R.T. (eds) Non-Protein Coding RNAs. Springer Series in Biophysics, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-70840-7_10

Download citation

Publish with us

Policies and ethics