Ribozymes, 2 Volume Set

Sabine Müller is Full Professor for Biochemistry/Bioorganic Chemistry at University Greifswald (Germany), and is a member of the Leibniz-Sozietät der Wissenschaften zu Berlin and of AcademiaNet. She has been working in the field of RNA engineering and has made important contributions to ribozyme research.Benoît Masquida is a Research Director at Centre National de la Recherche Scientifique, and carries on research and teaching activities at the University of Strasbourg (France). He made important contributions in the field of RNA structural biology, notably through identification of new RNA folds and their evolutionary relationships. Wade Winkler is Professor of Cell Biology and Molecular Genetics at the University of Maryland (USA), and has authored multiple influential publications on the different types of regulatory RNAs in bacteria.

• Volume 1Preface xviiForeword xixPart I Nucleic Acid Catalysis: Principles, Strategies and Biological Function 11 The Chemical Principles of RNA Catalysis 3Timothy J. Wilson and David M. J. Lilley1.1 RNA Catalysis 31.2 Rates of Chemical Reactions and Transition State Theory 41.3 Phosphoryl Transfer Reactions in the Ribozymes 51.4 Catalysis of Phosphoryl Transfer 61.5 General Acid–Base Catalysis in Nucleolytic Ribozymes 81.5.1 The Fraction of Active Catalyst, and the pH Dependence of Reaction Rates 91.5.2 The Reactivity of General Acids and Bases 131.6 pKa Shifting of General Acids and Bases in Nucleolytic Ribozymes 131.7 Catalytic Roles of Metal Ions in Ribozymes 141.8 The Choice Between General Acid–Base Catalysis and the Use of Metal Ions 171.9 The Limitations to RNA Catalysis 18Acknowledgment 18References 192 Biological Roles of Self-Cleaving Ribozymes 23Christina E. Weinberg2.1 Introduction 232.2 Use of Self-cleaving Ribozymes for Replication 252.2.1 Viroids 252.2.2 Viroid-like Satellite RNAs 282.2.3 Hepatitis δ Virus RNA 292.2.4 Neurospora Varkud Satellite RNAs Replicate Using a DNA Intermediate 292.3 Self-cleaving Ribozymes as Part of Transposable Elements 302.3.1 R2 Elements: Non-LTR Retrotransposons that Use HDV-like Ribozymes for Retrotransposition 302.3.2 HDV-like Ribozymes in Other Non-LTR Retrotransposon Lineages 342.3.3 Penelope-like Elements (PLEs) Contain Hammerhead Ribozymes 352.3.4 Hammerhead Ribozymes Associated with Repetitive Elements in Schistosoma mansoni 392.3.5 Retrozymes: A New Class of Plant Retrotransposons that Contains Hammerhead Ribozymes 402.4 Hammerhead Ribozymes with Suggested Roles in mRNA Biogenesis 412.5 The glmS Ribozyme Regulates Glucosamine-6-phosphate Levels in Bacteria 412.6 The Biological Roles of Many Ribozymes Are Unknown 422.7 Conclusion 43Acknowledgments 43References 44Part II Naturally Occurring Ribozymes 553 Chemical Mechanisms of the Nucleolytic Ribozymes 57Timothy J. Wilson and David M. J. Lilley3.1 The Nucleolytic Ribozymes 573.2 Some Nucleolytic Ribozymes AreWidespread 583.3 Secondary Structures of Nucleolytic Ribozymes – Junctions and Pseudoknots 583.4 Catalytic Players in the Nucleolytic Ribozymes 603.5 The Hairpin and VS Ribozymes: The G Plus A Mechanism 613.6 The Twister Ribozyme: A G Plus A Variant 663.7 The Hammerhead Ribozyme: A 2′-Hydroxyl as a Catalytic Participant 693.8 The Hepatitis Delta Virus Ribozyme: A Direct Role for a Metal Ion 723.9 The Twister Sister (TS) Ribozyme: Another Metallo-Ribozyme 743.10 The Pistol Ribozyme: A Metal Ion as the General Acid 763.11 The glmS Ribozyme: Participation of a Coenzyme 783.12 A Classification of the Nucleolytic Ribozymes Based on Catalytic Mechanism 79Acknowledgments 83References 834 TheglmS Ribozyme and Its Multifunctional Coenzyme Glucosamine-6-phosphate 91Juliane Soukup4.1 Introduction 914.2 Ribozymes 914.3 Riboswitches 924.4 The glmS Riboswitch/Ribozyme 934.5 Biological Function of the glmS Ribozyme 944.6 glmS Ribozyme Structure and Function – Initial Biochemical Analyses 954.7 glmS Ribozyme Structure and Function – Initial Crystallographic Analysis 984.8 Metal Ion Usage by the glmS Ribozyme 994.9 In Vitro Selected glmS Catalyst Loses Coenzyme Dependence 1014.10 Essential Coenzyme GlcN6P Functional Groups 1024.11 Mechanism of glmS Ribozyme Self-Cleavage 1044.11.1 Importance of Coenzyme GlcN6P 1044.11.2 pH-Reactivity Profiles 1064.11.3 Role of an Active Site Guanine 1084.12 Potential for Antibiotic Development Affecting glmS Ribozyme/Riboswitch Function 109Acknowledgments 110References 1105 The Lariat Capping Ribozyme 117Henrik Nielsen, Nicolai Krogh, Benoît Masquida, and Steinar Daae Johansen5.1 Introduction 1175.1.1 The Basics 1175.1.2 A Brief Account of the Discovery of the Lariat Capping Ribozyme 1195.1.3 Readers Guide to Nomenclature 1205.1.4 The Species Involved 1205.2 Reactions Catalyzed by LCrz 1215.2.1 The Branching Reaction 1225.2.2 Ligation and Hydrolysis 1225.2.3 Reaction Conditions 1245.3 The Structure of the LCrz Core 1255.3.1 The Detailed Structure of DirLCrz 1255.3.2 Structure of the Naegleria-type LCrz 1265.4 Communication Between LCrz and Flanking Elements 1285.4.1 Group I Ribozyme Switching 1285.4.2 LC Ribozyme Switching 1305.4.3 A Role of Spliceosomal Intron I51 in DirLCrz Regulation? 1315.5 Reflections on the Evolutionary Aspect of LCrz 1315.5.1 A Model for the Emergence of LCrz 1325.5.2 An Evolutionary Path to Spliceosomal Splicing? 1325.6 LCrz as a Research Tool 1345.7 Conclusions and Unsolved Problems 136References 1386 Self-Splicing Group II Introns 143Isabel Chillón and Marco Marcia6.1 Introduction 1436.2 Milestones in the Characterization of Group II Introns 1436.3 Evolutionary Conservation and Biological Role 1456.3.1 Phylogenetic Classifications 1456.3.2 Differentiation and Evolutionarily Acquired Properties 1486.3.3 Spreading and Survival in the Host Genome 1496.4 Structural Architecture 1526.4.1 Secondary Structure and Long-Range Tertiary Interactions 1526.4.2 Folding 1536.4.3 Stabilization by Solvent and IEP 1546.4.4 Active Site and Reaction Mechanism 1546.5 Lessons and Tools from Group II Intron Research 1566.5.1 Analogies to Other Splicing Machineries 1566.5.2 Lessons to Study Other Large Non-coding RNAs 1576.5.3 Biotechnological Applications of GIIi 1576.6 Perspectives and Open Questions 158Acknowledgments 158References 1587 The Spliceosome: an RNA–Protein Ribozyme Derived From Ancient Mobile Genetic Elements 169Erin L. Garside, Oliver A. Kent, and Andrew M. MacMillan7.1 Discovery of Introns and Splicing 1697.2 snRNPs and the Spliceosome 1707.3 The Spliceosomal Cycle 1717.4 Chemistry of Splicing 1737.5 Spliceosome Structural Analysis 1777.6 Spliceosome Structures 1777.6.1 Pre-spliceosome: Tri-snRNP 1777.6.2 Pre-spliceosome: A Complex 1797.6.3 B Complex 1797.6.4 Activated B Complex 1827.6.5 C and C* Complexes 1837.6.6 P Complex 1857.6.7 Intron Lariat Spliceosome Complex 1857.7 Insights from Spliceosome Disassembly 1877.8 Conservation of Spliceosomal and Group II Active Sites 1877.9 Summary and Perspectives 188References 1898 The Ribosome and Protein Synthesis 193Paul Huter, Michael Graf, and Daniel N. Wilson8.1 Central Dogma of Molecular Biology 1938.2 Structure of the E. coli Ribosome 1948.3 Translation Cycle 1948.3.1 Initiation 1968.3.2 Elongation 1998.3.3 Termination 2088.3.4 Recycling 211References 2139 The RNase P Ribozyme 227Markus Gößringer, Isabell Schencking, and Roland Karl Hartmann9.1 Introduction 2279.2 Bacterial RNase P 2299.2.1 P RNA Structure and Evolution 2299.2.2 The Single Protein Subunit 2339.2.3 P RNAs – Architectural Principles, Variations, Idiosyncrasies 2339.3 Substrate Interaction 2359.4 RNA-based Metal Ion Catalysis 2479.4.1 The Two-metal Ion Mechanism 2479.4.2 Architecture of the Active Site 2509.4.3 The “A248/nt −1” Interaction 2519.4.4 Specific RNase P Cleavage by the P15 Module 2539.5 RNase P as an Antibiotic Target 2549.5.1 P RNA as a Target 2549.5.2 The Bacterial RNase P Holoenzyme as Target 2579.5.3 P Protein as a Target 2589.6 Application of RNase P as a Tool in Gene Inactivation 2589.6.1 The Guide Sequence (GS) Concept 2589.6.2 EGS Technology in Eukaryotic Cells 2599.6.3 EGS Oligonucleotides and Recruitment of Human Nuclear-Cytoplasmic RNase P 2619.6.4 The M1–GS Approach 2659.6.5 Outlook 266References 26710 Ribozyme Discovery in Bacteria 281Adam Roth and Ronald Breaker10.1 Introduction 28110.2 Protein Takeover 28210.3 Ribozymes as Evolutionary Holdouts 28210.4 The Role of Serendipity in Early Ribozyme Discoveries 28310.5 Ribozymes Emerge from Structured Noncoding RNA Searches 28510.6 Ribozymes Beget Ribozymes 28910.7 Ribozyme Dispersal Driven by Association with Selfish Elements 29110.8 Domesticated Ribozymes 29210.9 New Ribozymes from Old 29410.10 Will New ncRNAs Broaden the Scope of RNA Catalysis? 295Acknowledgments 296References 29611 Small Self-Cleaving Ribozymes in the Genomes of Vertebrates 303Marcos de la Peña11.1 The Family of Small Self-Cleaving Ribozymes in Eukaryotic Genomes: From Retrotransposition to Domestication 30311.2 The Widespread Case of the Hammerhead Ribozyme: From Bacteria to Vertebrate Genomes 30411.2.1 The Discontinuous HHR in Mammals 30711.2.2 Intronic HHRs in Amniotes 31011.3 Other Intronic HHRs in Amniotes: Small Catalytic RNAs in Search of a Function 31511.4 The Family of the Hepatitis D Virus Ribozymes 31811.4.1 An Intronic HDV-Like Ribozyme Conserved in the Genome of Mammals 32011.5 Other Small Self-Cleaving Ribozymes Hidden in the Genomes of Vertebrates? 322References 323Part III Engineered Ribozymes 32912 Phosphoryl Transfer Ribozymes 331Razvan Cojocaru and Peter J. Unrau12.1 Introduction 33112.2 Kinase Ribozymes 33212.3 Glycosidic Bond Forming Ribozymes 33612.4 Capping Ribozymes 34012.5 Ligase Ribozymes 34412.6 Polymerase Ribozymes 35112.7 Summary 353References 35313 RNA Replication and the RNA Polymerase Ribozyme 359Falk Wachowius and Philipp Holliger13.1 Introduction 35913.2 Nonenzymatic RNA Polymerization 36013.3 Enzymatic RNA Polymerization 36113.4 Essential Requirements for an RNA Replicator 36313.4.1 Likelihood of Replicating Sequences in RNA Sequence Space 36413.4.2 Reaction Conditions for RNA Replication 36613.4.3 The Strand Separation Problem 36713.5 The Class I Ligase and the First RNA Polymerase Ribozymes 36713.6 Structural Insight into the Catalytic Core of the RNA Polymerase Ribozyme 37213.7 Selection for Improved Polymerase Activity I 37413.8 Selection for Improved Polymerase Activity II 37713.9 Conclusion and Outlook 380References 38114 Maintenance of Genetic Information in the First Ribocell 387Ádám Kun14.1 The Ribocell and the Stages of the RNAWorld 38714.1.1 Replication of the Genetic Information 38914.1.2 On the Metabolic Complexity of Ribocells 38914.2 The Error Thresholds 39114.2.1 Introducing the Error Threshold 39114.2.2 The Fitness Landscape and Neutrality of Mutations 39314.3 Compartmentalization 39614.3.1 Surface Metabolism and Transient Compartmentalization 39714.3.2 The Stochastic Corrector Model 39914.4 Minimal Gene Content of the First Ribocell 40114.4.1 Intermediate Metabolism 40214.4.2 Cell-Level Processes 404Acknowledgments 406References 40615 Ribozyme-Catalyzed RNA Recombination 419Benedict A. Smail and Niles Lehman15.1 Introduction 41915.2 RNA Recombination Chemistry 42015.3 Azoarcus Group I Intron 42115.4 Crystal Structure 42215.5 Mechanism 42215.6 Model for Prebiotic Chemistry 42315.7 Spontaneous Self-assembly of Azoarcus RNA Fragments 42515.8 Autocatalysis 42815.9 Cooperative Self-assembly 42915.10 Game Theoretic Treatment 43015.11 Significance of Game Theoretic Treatments 43215.12 Other Recombinase Ribozymes 43315.13 Conclusions 435References 43616 Engineering of Hairpin Ribozymes for RNA Processing Reactions 439Robert Hieronymus, Jikang Zhu, Bettina Appel, and Sabine Müller16.1 Introduction 43916.2 The Naturally Occurring Hairpin Ribozyme 44016.3 Structural Variants of the Hairpin Ribozyme 44216.4 Hairpin Ribozymes that are Regulated by External Effectors 44316.5 Twin Ribozymes for RNA Repair and Recombination 44616.6 Hairpin Ribozymes as RNA Recombinases 44916.7 Self-Splicing Hairpin Ribozymes 45216.8 Closing Remarks 454References 45617 Engineering of the Neurospora Varkud Satellite Ribozyme for Cleavage of Nonnatural Stem-Loop Substrates 463Pierre Dagenais, Julie Lacroix-Labonté, Nicolas Girard, and Pascale Legault17.1 Introduction 46317.2 Simple Primary and Secondary Structure Changes Compatible with Substrate Cleavage by the VS Ribozyme 46417.2.1 Circular Permutations and trans Cleavage 46417.2.2 The I/V Kissing-Loop Interaction and the Associated Conformational Change in SLI 46617.2.3 Summary of SLI Sequences Compatible with Cleavage by the Wild-Type VS Ribozyme 46817.3 The Structural Context 47017.3.1 NMR Investigations of the VS Ribozyme 47017.3.2 Crystal Structures of a Dimeric Form of the VS Ribozyme 47317.3.3 Open and Closed States of the S/R Complex 47317.4 Structure-Guided Engineering Studies 47417.4.1 Helix-Length Compensation 47417.4.2 Kissing-Loop Substitutions 47517.4.3 Role of KLI Dynamics in the Cleavage Reaction 47617.4.4 Improving the Cleavage Activity of a Designer Ribozyme 47817.5 Summary and Future Prospects for VS Ribozyme Engineering 480References 48118 Chemical Modifications in Natural and Engineered Ribozymes 487Stephanie Kath-Schorr18.1 Introduction 48718.2 Chemical Modifications to Study Natural Ribozymes 48818.2.1 Modified Nucleotides for Mechanistic and Structural Studies on Ribozymes 48818.2.2 Stabilization of Ribozymes by Chemical Modifications for in Cell Applications 48918.3 In Vitro Selection with Chemically Modified Nucleotides: Expanding the Scope of DNA and RNA Catalysis 49018.3.1 General Aspects for In Vitro Selection Using Unnatural Nucleotides 49118.3.2 Selection of Deoxyribozymes with Modified Nucleotides 49218.3.3 Artificial Ribozymes with Nonnatural Nucleobases 49418.3.4 Catalysts With Nonnatural Backbones: XNAzymes 49518.4 Outlook 495References 49619 Ribozymes for Regulation of Gene Expression 505Julia Stifel and Jörg S. Hartig19.1 Introduction 50519.2 Conditional Gene Expression Control by Riboswitches 50519.3 Allosteric Ribozymes as Engineered Riboswitches 50619.4 In Vitro Selection Methods 50719.5 In Vivo Screening Methods 50819.6 Rational Design of Allosteric Ribozymes 51119.7 Applications of Aptazymes for Gene Regulation 512References 51420 Development of Flexizyme Aminoacylation Ribozymes and Their Applications 519Takayuki Katoh, Yuki Goto, Toby Passioura, and Hiroaki Suga20.1 Introduction 51920.2 The First Ribozymes Catalyzing Acyl Transfer to RNAs 52020.3 The ATRib Variant Family: Ribozymes Catalyzing tRNA Aminoacylation via Self-Acylated Intermediates 52120.4 Prototype Flexizymes: Ribozymes Catalyzing Direct tRNA Aminoacylation 52320.5 Flexizymes: Versatile Ribozymes for the Preparation of Aminoacyl-tRNAs 52620.6 Application of Flexizymes to Genetic Code Reprogramming 52720.7 Development of Orthogonal tRNA/Ribosome Pairs Using Mutant Flexizymes 53020.8 In Vitro Selection of Bioactive Peptides Containing nPAAs Through RaPID Display 53220.9 tRid: A Method for Selective Removal of tRNAs from an RNA Pool 53520.10 Use of a Natural Small RNA Library Lacking tRNA for In Vitro Selection of a Folic Acid Aptamer: Small RNA Transcriptomic SELEX 53520.11 Summary and Perspective 537Acknowledgments 539References 53921 In Vitro Selected (Deoxy)ribozymes that Catalyze Carbon–Carbon Bond Formation 545Michael Famulok21.1 Introduction 54521.2 Diels–Alderase Ribozymes 54621.3 Aldolase Ribozyme 54721.4 A DNAzyme that Catalyzes a Friedel–Crafts Reaction 54821.5 Alkylating Ribozymes 55021.6 Conclusion 554References 55522 Nucleic Acid-Catalyzed RNA Ligation and Labeling 557Mohammad Ghaem Maghami and Claudia Höbartner22.1 Introduction 55722.2 Ribozymes for RNA Labeling at Internal Positions 55822.2.1 Fluorescein Iodoacetamide Reactive Ribozyme 55822.2.2 Genomically Derived Epoxide Reactive Ribozyme 55922.2.3 Twin Ribozyme 56122.2.4 DNA as a Catalyst for Ligation of Modified RNA 56222.2.5 Site-Specific Internal Labeling of RNA with DNA Enzymes 56322.3 RNA-Catalyzed Labeling of RNA at the 3′-end 56422.4 Potential Ribozymes for RNA Labeling at the 5′-end 56522.5 Conclusions 566Acknowledgments 566References 568Volume 2Preface xiiiForeword xvPart IV DNAzymes 57123 The Chemical Repertoire of DNA Enzymes 573Marcel Hollenstein24 Light-Utilizing DNAzymes 621Adam Barlev and Dipankar Sen25 Diverse Applications of DNAzymes in Computing and Nanotechnology 633Matthew R. Lakin, Darko Stefanovic, and Milan N. StojanovicPart V Ribozymes/DNAzymes in Diagnostics and Therapy 66126 Optimization of Antiviral Ribozymes 663Alfredo Berzal-Herranz and Cristina Romero-López27 DNAzymes as Biosensors 685Lingzi Ma and Juewen Liu28 Compartmentalization-Based Technologies for In Vitro Selection and Evolution of Ribozymes and Light-Up RNA Aptamers 721Farah Bouhedda and Michael RyckelynckPart VI Tools and Methods to Study Ribozymes 73929 Elucidation of Ribozyme Mechanisms at the Example of the Pistol Ribozyme 741Christoph Falschlunger, Josef Leiter, and Ronald Micura30 Strategies for Crystallization of Natural Ribozymes 753Benoît Masquida, Diana Sibrikova, and Maria Costa31 NMR Spectroscopic Investigation of Ribozymes 785Bozana Knezic, Oliver Binas, Albrecht Eduard Völklein, and Harald Schwalbe32 Studying Ribozymes with Electron Paramagnetic Resonance Spectroscopy 817Olav Schiemann33 Computational Modeling Methods for 3D Structure Prediction of Ribozymes 861Pritha Ghosh, Chandran Nithin, Astha Joshi, Filip Stefaniak, Tomasz K. Wirecki, and Janusz M. BujnickiIndex 883

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