Skip to main content
SpringerLink
Log in

Studying Parasite Gene Function and Interaction Through Ribozymes and Riboswitches Design Mechanism

  • Chapter
  • First Online:
Synthetic Biology

  • 938 Accesses

Abstract

Riboswitches are short mRNA sequences that can change their structural conformation to regulate the expression of adjacent genes. They regulate various biological processes via utilizing their secondary structure and consist of two distinct regions: (i) an evolutionarily conserved ligand-binding aptamer region and (ii) a variable expression platform regulating the gene expression. Many ligands bind to riboswitches, and its accurate and selective recognition requires a specific architecture that completely matches a given molecule. In general, the ligand-binding site can be found within the adjacent junction or regions; however, certain ligands may interact with the distant riboswitch regions. Gene expressions can be regulated by switching between two alternative RNA conformations; one of these conformations is favored in the presence of bound metabolite, while the other is favored in its absence. Riboswitches can regulate genes via metabolic pathways that are involved in the biosynthesis of vitamins, amino acids, and purines. In the present chapter, we aim to explain the structure, functions, and biological significance of these molecules.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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

References

  • Abreu-Goodger C, Merino E (2005) RibEx: a web server for locating riboswitches and other conserved bacterial regulatory elements. Nucleic Acids Res 33:W690–W692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anderson P, Monforte J, Tritz R, Nesbitt S, Hearst J, Hampel A (1994) Mutagenesis of the hairpin ribozyme. Nucleic Acids Res 22:1096–1100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Angelucci F, Dimastrogiovanni D, Boumis G, Brunori M, Miele AE, Saccoccia F, Bellelli A (2010) Mapping the catalytic cycle of Schistosoma mansoni thioredoxin glutathione reductase by X-ray crystallography. J Biol Chem 285:32557–32567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baird NJ, Ferre-D’Amare AR (2010) Idiosyncratically tuned switching behavior of riboswitch aptamer domains revealed by comparative small-angle X-ray scattering analysis. RNA 16:598–609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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  CAS  PubMed  PubMed Central  Google Scholar 

  • Barroso-delJesus A, Tabler M, Berzal-Herranz A (1999) Comparative kinetic analysis of structural variants of the hairpin ribozyme reveals further potential to optimize its catalytic performance. Antisense Nucleic Acid Drug Dev 9:433–440

    Article  CAS  PubMed  Google Scholar 

  • Been MD, Wickham GS (1997) Self-cleaving ribozymes of hepatitis delta virus RNA. Eur J Biochem 247:741–753

    Article  CAS  PubMed  Google Scholar 

  • Beisel CL, Smolke CD (2009) Design principles for riboswitch function. PLoS Comput Biol 5:e1000363

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bengert P, Dandekar T (2004) Riboswitch finder – a tool for identification of riboswitch RNAs. Nucleic Acids Res 32:W154–W159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berzal-Herranz A, Joseph S, Burke JM (1992) In vitro selection of active hairpin ribozymes by sequential RNA-catalyzed cleavage and ligation reactions. Genes Dev 6:129–134

    Article  CAS  PubMed  Google Scholar 

  • Berzal-Herranz A, Joseph S, Chowrira BM, Butcher SE, Burke JM (1993) Essential nucleotide sequences and secondary structure elements of the hairpin ribozyme. EMBO J 12:2567–2573

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bevilacqua PC (2003) Mechanistic considerations for general acid-base catalysis by RNA: revisiting the mechanism of the hairpin ribozyme. Biochemistry 42:2259–2265

    Article  CAS  PubMed  Google Scholar 

  • Blount KF, Uhlenbeck OC (2005) The structure-function dilemma of the hammerhead ribozyme. Annu Rev Biophys Biomol Struct 34:415–440

    Article  CAS  PubMed  Google Scholar 

  • Bouchard P, Legault P (2014) A remarkably stable kissing-loop interaction defines substrate recognition by the Neurospora Varkud Satellite ribozyme. RNA 20:1451–1464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brantl S (2004) Bacterial gene regulation: from transcription attenuation to riboswitches and ribozymes. Trends Microbiol 12:473–475

    Article  CAS  PubMed  Google Scholar 

  • Brantl S, Wagner EG (2002) An antisense RNA-mediated transcriptional attenuation mechanism functions in Escherichia coli. J Bacteriol 184:2740–2747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Breaker RR (2011) Prospects for riboswitch discovery and analysis. Mol Cell 43:867–879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Breaker RR, Gesteland RF, Cech TR, Atkins JF (2006) The RNA world. Cold Spring Harbor Laboratory Press, New York

    Google Scholar 

  • Butcher SE, Burke JM (1994) Structure-mapping of the hairpin ribozyme. Magnesium-dependent folding and evidence for tertiary interactions within the ribozyme-substrate complex. J Mol Biol 244:52–63

    Article  CAS  PubMed  Google Scholar 

  • Buzayan JM, Gerlach WL, Bruening G (1986) Non-enzymatic cleavage and ligation of RNAs complementary to a plant virus satellite RNA. Nature 323:349–353

    Article  CAS  Google Scholar 

  • Cech TR, Zaug AJ, Grabowski PJ (1981) In vitro splicing of the ribosomal RNA precursor of Tetrahymena: involvement of a guanosine nucleotide in the excision of the intervening sequence. Cell 27:487–496

    Article  CAS  PubMed  Google Scholar 

  • Chang TH, Huang HD, Wu LC, Yeh CT, Liu BJ, Horng JT (2009) Computational identification of riboswitches based on RNA conserved functional sequences and conformations. RNA 15:1426–1430

    Article  CAS  PubMed  PubMed Central  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  CAS  PubMed  Google Scholar 

  • Chi YI, Martick M, Lares M, Kim R, Scott WG, Kim SH (2008) Capturing hammerhead ribozyme structures in action by modulating general base catalysis. PLoS Biol 6:e234

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chowrira BM, Burke JM (1991) Binding and cleavage of nucleic acids by the “hairpin” ribozyme. Biochemistry 30:8518–8522

    Article  CAS  PubMed  Google Scholar 

  • Chowrira BM, Berzal-Herranz A, Burke JM (1991) Novel guanosine requirement for catalysis by the hairpin ribozyme. Nature 354:320–322

    Article  CAS  PubMed  Google Scholar 

  • Cochrane JC, Lipchock SV, Strobel SA (2007) Structural investigation of the GlmS ribozyme bound to its catalytic cofactor. Chem Biol 14:97–105

    Article  CAS  PubMed  Google Scholar 

  • Cochrane JC, Lipchock SV, Smith KD, Strobel SA (2009) Structural and chemical basis for glucosamine 6-phosphate binding and activation of the glmS ribozyme. Biochemistry 48:3239–3246

    Article  CAS  PubMed  Google Scholar 

  • Das SR, Piccirilli JA (2005) General acid catalysis by the hepatitis delta virus ribozyme. Nat Chem Biol 1:45–52

    Article  CAS  PubMed  Google Scholar 

  • de la Pena M, Garcia-Robles I (2010a) Ubiquitous presence of the hammerhead ribozyme motif along the tree of life. RNA 16:1943–1950

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • de la Pena M, Garcia-Robles I (2010b) Intronic hammerhead ribozymes are ultraconserved in the human genome. EMBO Rep 11:711–716

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • De la Pena M, Gago S, Flores R (2003) Peripheral regions of natural hammerhead ribozymes greatly increase their self-cleavage activity. EMBO J 22:5561–5570

    Article  PubMed  PubMed Central  Google Scholar 

  • Desai SK, Gallivan JP (2004) Genetic screens and selections for small molecules based on a synthetic riboswitch that activates protein translation. J Am Chem Soc 126:13247–13254

    Article  CAS  PubMed  Google Scholar 

  • DeYoung M, Siwkowski AM, Lian Y, Hampel A (1995) Catalytic properties of hairpin ribozymes derived from Chicory yellow mottle virus and arabis mosaic virus satellite RNAs. Biochemistry 34:15785–15791

    Article  CAS  PubMed  Google Scholar 

  • Ding Y, Chan CY, Lawrence CE (2004) Sfold web server for statistical folding and rational design of nucleic acids. Nucleic Acids Res 32:W135–W141

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dohno C, Kohyama I, Kimura M, Hagihara M, Nakatani K (2013) A synthetic riboswitch that operates using a rationally designed ligand-RNA pair. Angew Chem Int Ed Engl 52:9976–9979

    Article  CAS  PubMed  Google Scholar 

  • Duhamel J, Liu DM, Evilia C, Fleysh N, Dinter-Gottlieb G, Lu P (1996) Secondary structure content of the HDV ribozyme in 95% formamide. Nucleic Acids Res 24:3911–3917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eddy SR (1998) Profile hidden Markov models. Bioinformatics 14:755–763

    Article  CAS  PubMed  Google Scholar 

  • Eddy SR (2011) Accelerated profile HMM searches. PLoS Comput Biol 7:e1002195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eiler D, Wang J, Steitz TA (2014) Structural basis for the fast self-cleavage reaction catalyzed by the twister ribozyme. Proc Natl Acad Sci U S A 111:13028–13033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Epshtein V, Mironov AS, Nudler E (2003) The riboswitch-mediated control of sulfur metabolism in bacteria. Proc Natl Acad Sci U S A 100:5052–5056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Epstein LM, Gall JG (1987) Self-cleaving transcripts of satellite DNA from the newt. Cell 48:535–543

    Article  CAS  PubMed  Google Scholar 

  • Fedor MJ (2000) Structure and function of the hairpin ribozyme. J Mol Biol 297:269–291

    Article  CAS  PubMed  Google Scholar 

  • Feldstein PA, Buzayan JM, Bruening G (1989) Two sequences participating in the autolytic processing of satellite tobacco ringspot virus complementary RNA. Gene 82:53–61

    Article  CAS  PubMed  Google Scholar 

  • Feldstein PA, Buzayan JM, van Tol H, Gough GR, Gilham PT, Bruening G (1990) Specific association between an endoribonucleolytic sequence from a satellite RNA and a substrate analogue containing a 2′-5′phosphodiester. Proc Natl Acad Sci 87:2623–2627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferbeyre G, Smith JM, Cedergren R (1998) Schistosome satellite DNA encodes active hammerhead ribozymes. Mol Cell Biol 18:3880–3888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferre-D’Amare AR (2010) The glmS ribozyme: use of a small molecule coenzyme by a gene-regulatory RNA. Q Rev Biophys 43:423–447

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ferre-D’Amare AR, Scott WG (2010) Small self-cleaving ribozymes. Cold Spring Harb Perspect Biol 2:a003574

    PubMed  PubMed Central  Google Scholar 

  • Ferre-D’Amare AR, Zhou K, Doudna JA (1998) Crystal structure of a hepatitis delta virus ribozyme. Nature 395:567–574

    Article  PubMed  Google Scholar 

  • Flinders J, Dieckmann T (2001) A pH controlled conformational switch in the cleavage site of the VS ribozyme substrate RNA. J Mol Biol 308:665–679

    Article  CAS  PubMed  Google Scholar 

  • Forster AC, Davies C, Sheldon CC, Jeffries AC, Symons RH (1988) Self-cleaving viroid and newt RNAs may only be active as dimers. Nature 334:265–267

    Article  CAS  PubMed  Google Scholar 

  • Ganguly A, Thaplyal P, Rosta E, Bevilacqua PC, Hammes-Schiffer S (2014) Quantum mechanical/molecular mechanical free energy simulations of the self-cleavage reaction in the hepatitis delta virus ribozyme. J Am Chem Soc 136:1483–1496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gelfand MS, Mironov AA, Jomantas J, Kozlov YI, Perumov DA (1999) A conserved RNA structure element involved in the regulation of bacterial riboflavin synthesis genes. Trends Genet 15:439–442

    Article  CAS  PubMed  Google Scholar 

  • Grasby JA, Mersmann K, Singh M, Gait MJ (1995) Purine functional groups in essential residues of the hairpin ribozyme required for catalytic cleavage of RNA. Biochemistry 34:4068–4076

    Article  CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • Grundy FJ, Lehman SC, Henkin TM (2003) The L box regulon: lysine sensing by leader RNAs of bacterial lysine biosynthesis genes. Proc Natl Acad Sci U S A 100:12057–12062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo HC, Collins RA (1995) Efficient trans-cleavage of a stem-loop RNA substrate by a ribozyme derived from neurospora VS RNA. EMBO J 14:368–376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hampel A (1998) The hairpin ribozyme: discovery, two-dimensional model, and development for gene therapy. Prog Nucleic Acid Res Mol Biol 58:1–39

    CAS  PubMed  Google Scholar 

  • Hampel A, Cowan JA (1997) A unique mechanism for RNA catalysis: the role of metal cofactors in hairpin ribozyme cleavage. Chem Biol 4:513–517

    Article  CAS  PubMed  Google Scholar 

  • Hampel KJ, Tinsley MM (2006) Evidence for preorganization of the glmS ribozyme ligand binding pocket. Biochemistry 45:7861–7871

    Article  CAS  PubMed  Google Scholar 

  • Hampel A, Tritz R (1989) RNA catalytic properties of the minimum (-)sTRSV sequence. Biochemistry 28:4929–4933

    Article  CAS  PubMed  Google Scholar 

  • Hampel A, Tritz R, Hicks M, Cruz P (1990) ‘Hairpin’ catalytic RNA model: evidence for helices and sequence requirement for substrate RNA. Nucleic Acids Res 18:299–304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hartig JS (2010) Turning riboswitches loose. Chembiochem: Eur J Chem Biol 11:640–641

    Article  CAS  Google Scholar 

  • Haseloff J, Gerlach WL (1988) Simple RNA enzymes with new and highly specific endoribonuclease activities. Nature 334:585–591

    Article  CAS  PubMed  Google Scholar 

  • Haseloff J, Gerlach WL (1989) Sequences required for self-catalysed cleavage of the satellite RNA of tobacco ringspot virus. Gene 82:43–52

    Article  CAS  PubMed  Google Scholar 

  • Havill JT, Bhatiya C, Johnson SM, Sheets JD, Thompson JS (2014) A new approach for detecting riboswitches in DNA sequences. Bioinformatics 30:3012–3019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Joseph S, Burke JM (1993) Optimization of an anti-HIV hairpin ribozyme by in vitro selection. J Biol Chem 268:24515–24518

    CAS  PubMed  Google Scholar 

  • Joseph S, Berzal-Herranz A, Chowrira BM, Butcher SE, Burke JM (1993) Substrate selection rules for the hairpin ribozyme determined by in vitro selection, mutation, and analysis of mismatched substrates. Genes Dev 7:130–138

    Article  CAS  PubMed  Google Scholar 

  • Kath-Schorr S, Wilson TJ, Li NS, Lu J, Piccirilli JA, Lilley DM (2012) General acid-base catalysis mediated by nucleobases in the hairpin ribozyme. J Am Chem Soc 134:16717–16724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ke A, Zhou K, Ding F, Cate JH, Doudna JA (2004) A conformational switch controls hepatitis delta virus ribozyme catalysis. Nature 429:201–205

    Article  CAS  PubMed  Google Scholar 

  • Ketzer P, Kaufmann JK, Engelhardt S, Bossow S, von Kalle C, Hartig JS, Ungerechts G, Nettelbeck DM (2014) Artificial riboswitches for gene expression and replication control of DNA and RNA viruses. Proc Natl Acad Sci U S A 111:E554–E562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khvorova A, Lescoute A, Westhof E, Jayasena SD (2003) Sequence elements outside the hammerhead ribozyme catalytic core enable intracellular activity. Nat Struct Biol 10:708–712

    Article  CAS  PubMed  Google Scholar 

  • Klein DJ, Ferre-D’Amare AR (2006) Structural basis of glmS ribozyme activation by glucosamine-6-phosphate. Science 313:1752–1756

    Article  CAS  PubMed  Google Scholar 

  • Kuo MY, Sharmeen L, Dinter-Gottlieb G, Taylor J (1988) Characterization of self-cleaving RNA sequences on the genome and antigenome of human hepatitis delta virus. J Virol 62:4439–4444

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lai MM (1995) The molecular biology of hepatitis delta virus. Annu Rev Biochem 64:259–286

    Article  CAS  PubMed  Google Scholar 

  • Lambowitz AM, Belfort M (2015) Mobile bacterial group II introns at the crux of eukaryotic evolution. Microbiol Spectr 3:MDNA3-0050-2014

    PubMed  Google Scholar 

  • Lambowitz AM, Zimmerly S (2004) Mobile group II introns. Annu Rev Genet 38:1–35

    Article  CAS  PubMed  Google Scholar 

  • Lee KY, Lee BJ (2017) Structural and biochemical properties of novel self-cleaving ribozymes. Molecules 22:E678

    Article  PubMed  CAS  Google Scholar 

  • Li S, Lunse CE, Harris KA, Breaker RR (2015) Biochemical analysis of hatchet self-cleaving ribozymes. RNA 21:1845–1851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lian Y, De Young MB, Siwkowski A, Hampel A, Rappaport J (1999) The sCYMV1 hairpin ribozyme: targeting rules and cleavage of heterologous RNA. Gene Ther 6:1114–1119

    Article  CAS  PubMed  Google Scholar 

  • Lilley DM (2004) The Varkud satellite ribozyme. RNA 10:151–158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lincoln TA, Joyce GF (2009) Self-sustained replication of an RNA enzyme. Science 323:1229–1232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Wilson TJ, McPhee SA, Lilley DM (2014) Crystal structure and mechanistic investigation of the twister ribozyme. Nat Chem Biol 10:739–744

    Article  CAS  PubMed  Google Scholar 

  • Loh E, Dussurget O, Gripenland J, Vaitkevicius K, Tiensuu T, Mandin P, Repoila F, Buchrieser C, Cossart P, Johansson J (2009) A trans-acting riboswitch controls expression of the virulence regulator PrfA in Listeria monocytogenes. Cell 139:770–779

    Article  CAS  PubMed  Google Scholar 

  • Lorenz R, Bernhart SH, Honer Zu Siederdissen C, Tafer H, Flamm C, Stadler PF, Hofacker IL (2011) Vienna RNA package 2.0. Algorithm Mol Biol 6:26

    Article  Google Scholar 

  • Lu C, Smith AM, Fuchs RT, Ding F, Rajashankar K, Henkin TM, Ke A (2008) Crystal structures of the SAM-III/S(MK) riboswitch reveal the SAM-dependent translation inhibition mechanism. Nat Struct Mol Biol 15:1076–1083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lunse CE, Schmidt MS, Wittmann V, Mayer G (2011) Carba-sugars activate the glmS-riboswitch of Staphylococcus aureus. ACS Chem Biol 6:675–678

    Article  CAS  PubMed  Google Scholar 

  • Mandal M, Breaker RR (2004) Gene regulation by riboswitches. Nat Rev Mol Cell Biol 5:451–463

    Article  CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • Martick M, Scott WG (2006) Tertiary contacts distant from the active site prime a ribozyme for catalysis. Cell 126:309–320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martick M, Horan LH, Noller HF, Scott WG (2008) A discontinuous hammerhead ribozyme embedded in a mammalian messenger RNA. Nature 454:899–902

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McCarthy TJ, Plog MA, Floy SA, Jansen JA, Soukup JK, Soukup GA (2005) Ligand requirements for glmS ribozyme self-cleavage. Chem Biol 12:1221–1226

    Article  CAS  PubMed  Google Scholar 

  • McCown PJ, Roth A, Breaker RR (2011) An expanded collection and refined consensus model of glmS ribozymes. RNA 17:728–736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Michel F, Ferat JL (1995) Structure and activities of group II introns. Annu Rev Biochem 64:435–461

    Article  CAS  PubMed  Google Scholar 

  • Michel F, Jacquier A, Dujon B (1982) Comparison of fungal mitochondrial introns reveals extensive homologies in RNA secondary structure. Biochimie 64:867–881

    Article  CAS  PubMed  Google Scholar 

  • Michiels PJ, Schouten CH, Hilbers CW, Heus HA (2000) Structure of the ribozyme substrate hairpin of Neurospora VS RNA: a close look at the cleavage site. RNA 6:1821–1832

    Article  CAS  PubMed  PubMed Central  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  CAS  PubMed  PubMed Central  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  CAS  PubMed  Google Scholar 

  • Mukherjee S, Sengupta S (2016) Riboswitch scanner: an efficient pHMM-based web-server to detect riboswitches in genomic sequences. Bioinformatics 32:776–778

    Article  CAS  PubMed  Google Scholar 

  • Muranaka N, Yokobayashi Y (2010) A synthetic riboswitch with chemical band-pass response. Chem Commun (Camb) 46:6825–6827

    Article  CAS  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  CAS  PubMed  Google Scholar 

  • Nakano S, Chadalavada DM, Bevilacqua PC (2000) General acid-base catalysis in the mechanism of a hepatitis delta virus ribozyme. Science 287:1493–1497

    Article  CAS  PubMed  Google Scholar 

  • Nesbitt S, Hegg LA, Fedor MJ (1997) An unusual pH-independent and metal-ion-independent mechanism for hairpin ribozyme catalysis. Chem Biol 4:619–630

    Article  CAS  PubMed  Google Scholar 

  • Nguyen LA, Wang J, Steitz TA (2017) Crystal structure of pistol, a class of self-cleaving ribozyme. Proc Natl Acad Sci U S A 114:1021–1026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nissen P, Hansen J, Ban N, Moore PB, Steitz TA (2000) The structural basis of ribosome activity in peptide bond synthesis. Science 289:920–930

    Article  CAS  PubMed  Google Scholar 

  • Nudler E (2006) Flipping riboswitches. Cell 126:19–22

    Article  CAS  PubMed  Google Scholar 

  • Nudler E, Mironov AS (2004) The riboswitch control of bacterial metabolism. Trends Biochem Sci 29:11–17

    Article  CAS  PubMed  Google Scholar 

  • Orelle C, Carlson ED, Szal T, Florin T, Jewett MC, Mankin AS (2015) Protein synthesis by ribosomes with tethered subunits. Nature 524:119–124

    Article  CAS  PubMed  Google Scholar 

  • Peebles CL, Perlman PS, Mecklenburg KL, Petrillo ML, Tabor JH, Jarrell KA, Cheng HL (1986) A self-splicing RNA excises an intron lariat. Cell 44:213–223

    Article  CAS  PubMed  Google Scholar 

  • Perez-Ruiz M, Barroso-DelJesus A, Berzal-Herranz A (1999) Specificity of the hairpin ribozyme. Sequence requirements surrounding the cleavage site. J Biol Chem 274:29376–29380

    Article  CAS  PubMed  Google Scholar 

  • Perreault J, Weinberg Z, Roth A, Popescu O, Chartrand P, Ferbeyre G, Breaker RR (2011) Identification of hammerhead ribozymes in all domains of life reveals novel structural variations. PLoS Comput Biol 7:e1002031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Perrotta AT, Been MD (1996) Core sequences and a cleavage site wobble pair required for HDV antigenomic ribozyme self-cleavage. Nucleic Acids Res 24:1314–1321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prody GA, Bakos JT, Buzayan JM, Schneider IR, Bruening G (1986) Autolytic processing of dimeric plant virus satellite RNA. Science 231:1577–1580

    Article  CAS  PubMed  Google Scholar 

  • Pyle AM (2005) Capping by branching: a new ribozyme makes tiny lariats. Science 309:1530–1531

    Article  CAS  PubMed  Google Scholar 

  • Pyle AM (2010) The tertiary structure of group II introns: implications for biological function and evolution. Crit Rev Biochem Mol Biol 45:215–232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rastogi T, Beattie TL, Olive JE, Collins RA (1996) A long-range pseudoknot is required for activity of the Neurospora VS ribozyme. EMBO J 15:2820–2825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren A, Kosutic M, Rajashankar KR, Frener M, Santner T, Westhof E, Micura R, Patel DJ (2014) In-line alignment and Mg(2)(+) coordination at the cleavage site of the env22 twister ribozyme. Nat Commun 5:5534

    Article  CAS  PubMed  Google Scholar 

  • Ren A, Vusurovic N, Gebetsberger J, Gao P, Juen M, Kreutz C, Micura R, Patel DJ (2016) Pistol ribozyme adopts a pseudoknot fold facilitating site-specific in-line cleavage. Nat Chem Biol 12:702–708

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Robart AR, Zimmerly S (2005) Group II intron retroelements: function and diversity. Cytogenet Genome Res 110:589–597

    Article  CAS  PubMed  Google Scholar 

  • Rodionov DA, Vitreschak AG, Mironov AA, Gelfand MS (2002) Comparative genomics of thiamin biosynthesis in procaryotes. New genes and regulatory mechanisms. J Biol Chem 277:48949–48959

    Article  CAS  PubMed  Google Scholar 

  • Rosenstein SP, Been MD (1990) Self-cleavage of hepatitis delta virus genomic strand RNA is enhanced under partially denaturing conditions. Biochemistry 29:8011–8016

    Article  CAS  PubMed  Google Scholar 

  • Roth A, Breaker RR (2009) The structural and functional diversity of metabolite-binding riboswitches. Annu Rev Biochem 78:305–334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roth A, Nahvi A, Lee M, Jona I, Breaker RR (2006) Characteristics of the glmS ribozyme suggest only structural roles for divalent metal ions. RNA 12:607–619

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roth A, Weinberg Z, Chen AG, Kim PB, Ames TD, Breaker RR (2013) A widespread self-cleaving ribozyme class is revealed by bioinformatics. Nat Chem Biol 10:56–60

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rubino L, Tousignant ME, Steger G, Kaper JM (1990) Nucleotide sequence and structural analysis of two satellite RNAs associated with chicory yellow mottle virus. J Gen Virol 71(Pt 9):1897–1903

    Article  CAS  PubMed  Google Scholar 

  • Ruffner DE, Stormo GD, Uhlenbeck OC (1990) Sequence requirements of the hammerhead RNA self-cleavage reaction. Biochemistry 29:10695–10702

    Article  CAS  PubMed  Google Scholar 

  • Rupert PB, Ferre-D’Amare AR (2001) Crystal structure of a hairpin ribozyme-inhibitor complex with implications for catalysis. Nature 410:780–786

    Article  CAS  PubMed  Google Scholar 

  • Ryder SP, Strobel SA (1999) Nucleotide analog interference mapping of the hairpin ribozyme: implications for secondary and tertiary structure formation. J Mol Biol 291:295–311

    Article  CAS  PubMed  Google Scholar 

  • Salehi-Ashtiani K, Luptak A, Litovchick A, Szostak JW (2006) A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene. Science 313:1788–1792

    Article  CAS  PubMed  Google Scholar 

  • Saville BJ, Collins RA (1990) A site-specific self-cleavage reaction performed by a novel RNA in Neurospora mitochondria. Cell 61:685–696

    Article  CAS  PubMed  Google Scholar 

  • Saville BJ, Collins RA (1991) RNA-mediated ligation of self-cleavage products of a Neurospora mitochondrial plasmid transcript. Proc Natl Acad Sci U S A 88:8826–8830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmelzer C, Schweyen RJ (1986) Self-splicing of group II introns in vitro: mapping of the branch point and mutational inhibition of lariat formation. Cell 46:557–565

    Article  CAS  PubMed  Google Scholar 

  • Schmidt S, Beigelman L, Karpeisky A, Usman N, Sorensen US, Gait MJ (1996) Base and sugar requirements for RNA cleavage of essential nucleoside residues in internal loop B of the hairpin ribozyme: implications for secondary structure. Nucleic Acids Res 24:573–581

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scott WG (2007) Ribozymes. Curr Opin Struct Biol 17:280–286

    Article  CAS  PubMed  Google Scholar 

  • Scott WG, Martick M, Chi YI (2009) Structure and function of regulatory RNA elements: ribozymes that regulate gene expression. Biochim Biophys Acta 1789:634–641

    Article  CAS  PubMed  Google Scholar 

  • Seehafer C, Kalweit A, Steger G, Graf S, Hammann C (2010) From alpaca to zebrafish: hammerhead ribozymes wherever you look. RNA 17:21–26

    Article  PubMed  CAS  Google Scholar 

  • Sekiguchi A, Komatsu Y, Koizumi M, Ohtsuka E (1991) Mutagenesis and self-ligation of the self-cleavage domain of the satellite RNA minus strand of tobacco ringspot virus and its binding to polyamines. Nucleic Acids Res 19:6833–6838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Serganov A, Patel DJ (2009) Amino acid recognition and gene regulation by riboswitches. Biochim Biophys Acta 1789:592–611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharmeen L, Kuo MY, Dinter-Gottlieb G, Taylor J (1988) Antigenomic RNA of human hepatitis delta virus can undergo self-cleavage. J Virol 62:2674–2679

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shih IH, Been MD (2002) Catalytic strategies of the hepatitis delta virus ribozymes. Annu Rev Biochem 71:887–917

    Article  CAS  PubMed  Google Scholar 

  • Shippy R, Siwkowski A, Hampel A (1998) Mutational analysis of loops 1 and 5 of the hairpin ribozyme. Biochemistry 37:564–570

    Article  CAS  PubMed  Google Scholar 

  • Silverman SK (2003) Rube Goldberg goes (ribo)nuclear? Molecular switches and sensors made from RNA. RNA 9:377–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siwkowski A, Shippy R, Hampel A (1997) Analysis of hairpin ribozyme base mutations in loops 2 and 4 and their effects on cis-cleavage in vitro. Biochemistry 36:3930–3940

    Article  CAS  PubMed  Google Scholar 

  • Siwkowski A, Humphrey M, De-Young MB, Hampel A (1998) Screening for important base identities in the hairpin ribozyme by in vitro selection for cleavage. BioTechniques 24:278–284

    Article  CAS  PubMed  Google Scholar 

  • Stahley MR, Strobel SA (2005) Structural evidence for a two-metal-ion mechanism of group I intron splicing. Science 309:1587–1590

    Article  CAS  PubMed  Google Scholar 

  • Steitz TA, Moore PB (2003) RNA, the first macromolecular catalyst: the ribosome is a ribozyme. Trends Biochem Sci 28:411–418

    Article  CAS  PubMed  Google Scholar 

  • Stormo GD, Ji Y (2001) Do mRNAs act as direct sensors of small molecules to control their expression? Proc Natl Acad Sci U S A 98:9465–9467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strobel SA, Cochrane JC (2007) RNA catalysis: ribozymes, ribosomes, and riboswitches. Curr Opin Chem Biol 11:636–643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sudarsan N, Hammond MC, Block KF, Welz R, Barrick JE, Roth A, Breaker RR (2006) Tandem riboswitch architectures exhibit complex gene control functions. Science 314:300–304

    Article  CAS  PubMed  Google Scholar 

  • Suh YA, Kumar PK, Taira K, Nishikawa S (1993) Self-cleavage activity of the genomic HDV ribozyme in the presence of various divalent metal ions. Nucleic Acids Res 21:3277–3280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Suslov NB, DasGupta S, Huang H, Fuller JR, Lilley DM, Rice PA, Piccirilli JA (2015) Crystal structure of the Varkud satellite ribozyme. Nat Chem Biol 11:840–846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Talini G, Gallori E, Maurel MC (2009) Natural and unnatural ribozymes: back to the primordial RNA world. Res Microbiol 160:457–465

    Article  CAS  PubMed  Google Scholar 

  • Tang J, Breaker RR (2000) Structural diversity of self-cleaving ribozymes. Proc Natl Acad Sci U S A 97:5784–5789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanner NK, Schaff S, Thill G, Petit-Koskas E, Crain-Denoyelle AM, Westhof E (1994) A three-dimensional model of hepatitis delta virus ribozyme based on biochemical and mutational analyses. Curr Biol 4:488–498

    Article  CAS  PubMed  Google Scholar 

  • Teixeira A, Tahiri-Alaoui A, West S, Thomas B, Ramadass A, Martianov I, Dye M, James W, Proudfoot NJ, Akoulitchev A (2004) Autocatalytic RNA cleavage in the human beta-globin pre-mRNA promotes transcription termination. Nature 432:526–530

    Article  CAS  PubMed  Google Scholar 

  • Thill G, Vasseur M, Tanner NK (1993) Structural and sequence elements required for the self-cleaving activity of the hepatitis delta virus ribozyme. Biochemistry 32:4254–4262

    Article  CAS  PubMed  Google Scholar 

  • Topp S, Gallivan JP (2007) Guiding bacteria with small molecules and RNA. J Am Chem Soc 129:6807–6811

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toro N, Jimenez-Zurdo JI, Garcia-Rodriguez FM (2007) Bacterial group II introns: not just splicing. FEMS Microbiol Rev 31:342–358

    Article  CAS  PubMed  Google Scholar 

  • Uhlenbeck OC (1987) A small catalytic oligoribonucleotide. Nature 328:596–600

    Article  CAS  PubMed  Google Scholar 

  • Valadkhan S (2007) The spliceosome: a ribozyme at heart? Biol Chem 388:693–697

    Article  CAS  PubMed  Google Scholar 

  • Veeraraghavan N, Ganguly A, Golden BL, Bevilacqua PC, Hammes-Schiffer S (2011) Mechanistic strategies in the HDV ribozyme: chelated and diffuse metal ion interactions and active site protonation. J Phys Chem B 115:8346–8357

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vogel J, Wagner EG (2007) Target identification of small noncoding RNAs in bacteria. Curr Opin Microbiol 10:262–270

    Article  CAS  PubMed  Google Scholar 

  • Webb CH, Riccitelli NJ, Ruminski DJ, Luptak A (2009) Widespread occurrence of self-cleaving ribozymes. Science 326:953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Weinberg Z, Wang JX, Bogue J, Yang J, Corbino K, Moy RH, Breaker RR (2010) Comparative genomics reveals 104 candidate structured RNAs from bacteria, archaea, and their metagenomes. Genome Biol 11:R31

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Weinberg Z, Kim PB, Chen TH, Li S, Harris KA, Lunse CE, Breaker RR (2015) New classes of self-cleaving ribozymes revealed by comparative genomics analysis. Nat Chem Biol 11:606–610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Werstuck G, Green MR (1998) Controlling gene expression in living cells through small molecule-RNA interactions. Science 282:296–298

    Article  CAS  PubMed  Google Scholar 

  • Wieland M, Hartig JS (2008) Artificial riboswitches: synthetic mRNA-based regulators of gene expression. Chembiochem: Eur J Chem Biol 9:1873–1878

    Article  CAS  Google Scholar 

  • Wilson TJ, Lilley DM (2010) Do the hairpin and VS ribozymes share a common catalytic mechanism based on general acid-base catalysis? A critical assessment of available experimental data. RNA 17:213–221

    Article  PubMed  CAS  Google Scholar 

  • Wilson TJ, McLeod AC, Lilley DM (2007) A guanine nucleobase important for catalysis by the VS ribozyme. EMBO J 26:2489–2500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Winkler W, Nahvi A, Breaker RR (2002) Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. Nature 419:952–956

    Article  CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • Wu HN, Lin YJ, Lin FP, Makino S, Chang MF, Lai MM (1989) Human hepatitis delta virus RNA subfragments contain an autocleavage activity. Proc Natl Acad Sci U S A 86:1831–1835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xin Y, Hamelberg D (2010) Deciphering the role of glucosamine-6-phosphate in the riboswitch action of glmS ribozyme. RNA 16:2455–2463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yanofsky C (1981) Attenuation in the control of expression of bacterial operons. Nature 289:751–758

    Article  CAS  PubMed  Google Scholar 

  • Young KJ, Gill F, Grasby JA (1997) Metal ions play a passive role in the hairpin ribozyme catalysed reaction. Nucleic Acids Res 25:3760–3766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Young KJ, Vyle JS, Pickering TJ, Cohen MA, Holmes SC, Merkel O, Grasby JA (1999) The role of essential pyrimidines in the hairpin ribozyme-catalysed reaction. J Mol Biol 288:853–866

    Article  CAS  PubMed  Google Scholar 

  • Zhang S, Ganguly A, Goyal P, Bingaman JL, Bevilacqua PC, Hammes-Schiffer S (2014) Role of the active site guanine in the glmS ribozyme self-cleavage mechanism: quantum mechanical/molecular mechanical free energy simulations. J Am Chem Soc 137:784–798

    Article  PubMed Central  CAS  Google Scholar 

  • Zimmerly S, Semper C (2015) Evolution of group II introns. Mob DNA 6:7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • zu Putlitz J, Yu Q, Burke JM, Wands JR (1999) Combinatorial screening and intracellular antiviral activity of hairpin ribozymes directed against hepatitis B virus. J Virol 73:5381–5387

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Molecular and Structural Biophysics Laboratory, Department of Biochemistry, North-Eastern Hill University, Shillong, India

    Harish Shukla & Timir Tripathi

Authors
  1. Harish Shukla
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Timir Tripathi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Timir Tripathi .

Editor information

Editors and Affiliations

  1. Department of Pathogenesis and Cellular Response, National Centre for Cell Science, Computational and Systems Biology Lab, Pune, Maharashtra, India

    Shailza Singh

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Shukla, H., Tripathi, T. (2018). Studying Parasite Gene Function and Interaction Through Ribozymes and Riboswitches Design Mechanism. In: Singh, S. (eds) Synthetic Biology. Springer, Singapore. https://doi.org/10.1007/978-981-10-8693-9_4

Download citation

Publish with us

Policies and ethics

Search

Navigation