Many Faces of RNA [Hardback]

Contributors xi(2) Introduction xiii I OVERVIEW 1(18) 1 RNA as a Therapeutic Target for Bleomycin 3(16) S.M. Hecht Abstract 3(1) 1 Introduction 4(2) 2 RNAs that are cleaved by bleomycin in vitro 6(5) 3 Cleavage of a DNA-RNA heteroduplex by Fe Bleomycin 11(1) 4 Structural factors controlling the cleavage of DNA and RNA 11(2) 5 Cleavage of RNA by bleomycin in an intact cell 13(2) 6 The case for RNA as a therapeutic target for BLM 15(1) 7 Conclusion 15(1) Acknowledgement 16(1) References 16(3) II RNA: CHEMISTRY, STRUCTURE AND INTERACTIONS 19(64) 2 Synthetic RNA Modification and Cross-linking Approaches towards the Structure of the Hairpin Ribozyme and the HIV-1 Tat Protein Interaction with TAR RNA 21(20) M.J. Gait D.J. Earnshaw M.A. Farrow N.A. Naryshkin Abstract 21(1) 1 Introduction 22(1) 2 Chemical synthesis of oligoribonucleotides and analogues 23(5) 3 The hairpin ribozyme 28(3) 4 HIV-1 Tat protein interaction with TAR RNA 31(4) Acknowledgements 35(1) References 36(5) 3 The Ribosome -- The Universal Protein-synthesizing Machine 41(14) R. Brimacombe Abstract 41(1) 1 Introduction 42(1) 2 The new era in electron microscopy 43(1) 3 Three-dimensional modelling of the ribosomal RNA 44(2) 4 RNA-protein interactions 46(1) 5 The decoding region of the 30 S subunit 47(3) 6 Sites of interaction with antibiotics 50(1) 7 Conclusions 51(1) References 51(4) 4 tRNA Recognition by Aminoacyl-tRNA Synthetases 55(12) S. Cusack A. Yaremchuk M. Tukalo Abstract 55(1) 1 Introduction 55(1) 2 tRNA identity 56(1) 3 The two classes of aminoacyl-tRNA synthetases 57(1) 4 RNA-binding modules in aminoacyl-tRNA synthetases 57(2) 5 General features of tRNA recognition by aminoacyl-tRNA synthetases 59(1) 6 Glutaminyl-tRNA synthetase (GlnRS) 59(1) 7 tRNA recognition by class IIb synthetases 60(1) 8 tRNA recognition by class IIa aminoacyl-tRNA synthetases 61(2) 9 Seryl-tRNA synthetase (SerRS) 63(1) Acknowledgements 64(1) References 64(3) 5 RNA-Protein Recognition During RNA Processing and Maturation 67(16) G. Varani Abstract 67(1) 1 Introduction 67(1) 2 RNA recognition differs from DNA recognition 68(2) 3 XXX protein domains 70(2) 4 The RNP domain paradigm of RNA recognition 72(1) 5 RNP proteins recognize both the identity of single-stranded nucleotides and the unique shape and charge distribution of the substrate RNA 73(4) 6 Rigid docking and adaptive binding 77(1) 7 Conformational flexibility at RNA-protein interfaces 78(1) 8 Do RNA and protein conformational rearrangements contribute to specificity? 79(1) 9 Functional implications 79(1) 10 Conclusions and perspectives 80(1) Acknowledgements 80(1) References 80(3) III RNA AS A TARGET/RNA AS A TOOL 83(108) 6 Exploiting RNA: Potential Targets, Screens and Drug Development 85(12) C.D. Prescott L. Hegg K. Nurse R. Gontarek Hu Li V. Emerick T. Sterner M. Gress G. Thom S. Guth D. Rispoli Abstract 85(1) 1 Introduction 86(1) 2 Validity of RNA as a target 86(1) 3 Target selection: criteria and issues 87(1) 4 Exploiting RNA as a target and tool 88(5) 5 Concluding remarks 93(1) References 93(4) 7 Structural Basis for Aminoglycoside Antibiotic Action 97(16) J.D. Puglisi Abstract 97(1) 1 Introduction 98(2) 2 Aminoglycoside antibiotics 100(1) 3 Defining a model oligonucleotide for structural studies 101(2) 4 RNA structure determination by NMR 103(2) 5 Conformation of the unbound A-site RNA 105(1) 6 Structure of the A-site RNA-paromomycin complex 105(2) 7 Prokaryotic specificity of aminoglycoside antibiotics 107(1) 8 Structure explains resistance mechanisms 108(2) 9 Mechanism of aminoglycoside-induced miscoding 110(1) 10 Conclusions 110(1) Acknowledgements 111(1) References 111(2) 8 Protein-RNA Recognition in a Highly Conserved Ribosomal Domain Targeted by Thiazole Antibiotics 113(14) D.E. Draper Abstract 113(1) 1 Introduction 114(1) 2 Structure of the RNA binding domain of ribosomal protein L11 115(2) 3 An RNA tertiary structure dependent on Mg(2+) and NH(4)(+) ions 117(3) 4 RNA features required for protein recognition 120(2) 5 Targeting of thiazole antibiotics to the L11-RNA complex 122(1) 6 Conclusions 123(1) Acknowledgements 124(1) References 124(3) 9 RNase P and Its Substrate 127(18) L.A. Kirsebom Abstract 127(1) 1 Introduction 128(1) 2 RNase P RNA-substrate interactions 129(8) 3 RNase P RNA structure and function 137(3) 4 Summary 140(1) 5 Concluding remarks 141(1) Acknowledgements 141(1) References 141(4) 10 Interfering with Gene Function at the RNA Level with Oligozymes-the Development of New Tools and Therapeutics 145(16) B.S. Sproat S.T. George M. Ma A.R. Goldberg Abstract 145(1) 1 Introduction 146(2) 2 Oligozymes 148(3) 3 Oligozymes based on the hammerhead ribozyme 151(2) 4 Choosing a target site on an RNA 153(2) 5 Elucidating gene function in vivo 155(2) 6 Conclusion 157(1) References 158(3) 11 Progress towards Therapeutic Application of SELEX-derived Aptamers 161(18) B. Polisky Abstract 161(1) 1 Introduction 162(3) 2 Design and construction of an oligonucleotide library 165(2) 3 Partition 167(3) 4 Truncation 170(1) 5 Post-SELEX modifications 171(1) 6 Aptamer structures 171(1) 7 Applications 172(2) 8 Conclusion and perspective 174(1) Acknowledgements 175(1) References 175(4) 12 Catalysis of Organic Reactions by RNA-Strategies for the Selection of Catalytic RNAs 179(12) A. Jaschke Abstract 179(1) 1 Introduction 180(1) 2 Selection of catalytic RNA molecules 181(2) 3 SELEX with linker-coupled reactants 183(4) 4 Future directions 187(2) Acknowledgement 189(1) References 189(2) Conclusions and Opportunities 191(4) B.W. Metcalf Appendix: Abstracts of Posters 195(28) Index 223