The Many Faces of RNA

Eggleston, D. S.; Prescott, Catherine D.; Pearson, Neil D.

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Table of contents
  • Contentsv
  • Contributorsxi
  • Introductionxiii
  • PART I: OVERVIEW1
  • Chapter 1. RNA as a Therapeutic Target for Bleomycin3
  • Abstract3
  • 1 Introduction4
  • 2 RNAs that are cleaved by bleomycin in vitro6
  • 3 Cleavage of a DNA-RNA heteroduplex by Fe-Bleomycin11
  • 4 Structural factors controlling the cleavage of DNA and RNA11
  • 5 Cleavage of RNA by bleomycin in an intact cell13
  • 6 The case for RNA as a therapeutic target for BLM15
  • 7 Conclusion15
  • Acknowledgement16
  • References16
  • PART II: RNA: CHEMISTRY, STRUCTURE AND INTERACTIONS19
  • Chapter 2. Synthetic RNA Modification and Cross-linking Approaches towards the Structure of the Hair21
  • Abstract21
  • 1 Introduction22
  • 2 Chemical synthesis of oligoribonucleotides and analogues23
  • 3 The hairpin ribozyme28
  • 4 HIV-1 Tat protein interaction with TAR RNA31
  • Acknowledgements35
  • References36
  • Chapter 3. The Ribosome - The Universal Protein-synthesizing Machine41
  • Abstract41
  • 1 Introduction42
  • 2 The new era in electron microscopy43
  • 3 Three-dimensional modelling of the ribosomal RNA44
  • 4 RNA-protein interactions46
  • 5 The decoding region of the 30 S subunit47
  • 6 Sites of interaction with antibiotics50
  • 7 Conclusions51
  • References51
  • Chapter 4. tRNA Recognition by Aminoacyl-tRNA Synthetases*55
  • Abstract55
  • 1 Introduction55
  • 2 tRNA identity56
  • 3 The two classes of aminoacyl-tRNA synthetases57
  • 4 RNA-binding modules in aminoacyl-tRNA synthetases57
  • 5 General features of tRNA recognition by aminoacyl-tRNA synthetases59
  • 6 Glutaminyl-tRNA synthetase (GlnRS)59
  • 7 tRNA recognition by class IIb synthetases60
  • 8 tRNA recognition by class Ila aminoacyl-tRNA synthetases61
  • 9 Seryl-tRNA synthetase (SerRS)63
  • Acknowledgements64
  • References64
  • Chapter 5. RNA-Protein Recognition During RNA Processing and Maturation*67
  • Abstract67
  • 1 Introduction67
  • 2 RNA recognition differs from DNA recognition68
  • 3 aB protein domains70
  • 4 The RNP domain paradigm of RNA recognition72
  • 5 RNP proteins recognize both the identity of single-stranded nucleotides and the unique shape and c73
  • 6 Rigid docking and adaptive binding77
  • 7 Conformational flexibility at RNA-protein interfaces78
  • 8 Do RNA and protein conformational rearrangements contribute to specificity?79
  • 9 Functional implications79
  • 10 Conclusions and perspectives80
  • Acknowledgements80
  • References80
  • PART III: RNA AS A TARGET/RNA AS A TOOL83
  • Chapter 6. Exploiting RNA: Potential Targets, Screens and Drug Development85
  • Abstract85
  • 1 Introduction86
  • 2 Validity of RNA as a target86
  • 3 Target selection: criteria and issues87
  • 4 Exploiting RNA as a target and tool88
  • 5 Concluding remarks93
  • References93
  • Chapter 7. Structural Basis for Aminoglycoside Antibiotic Action*97
  • Abstract97
  • 1 Introduction98
  • 2 Aminoglycoside antibiotics100
  • 3 Defining a model oligonucleotide for structural studies101
  • 4 RNA structure determination by NMR103
  • 5 Conformation of the unbound A-site RNA105
  • 6 Structure of the A-site RNA-paromomycin complex105
  • 7 Prokaryotic specificity of aminoglycoside antibiotics107
  • 8 Structure explains resistance mechanisms108
  • 9 Mechanism of aminoglycoside-induced miscoding110
  • 10 Conclusions110
  • Acknowledgements111
  • References111
  • Chapter 8. Protein-RNA Recognition in a Highly Conserved Ribosomal Domain Targeted by Thiazole Antib113
  • Abstract113
  • 1 Introduction114
  • 2 Structure of the RNA binding domain of ribosomal protein L11115
  • 3 An RNA tertiary structure dependent on Mg2+ and NH4+ ions117
  • 4 RNA features required for protein recognition120
  • 5 Targeting of thiazole antibiotics to the L11-RNA complex122
  • 6 Conclusions123
  • Acknowledgements124
  • References124
  • Chapter 9. RNase P and Its Substrate*127
  • Abstract127
  • 1 Introduction128
  • 2 RNase P RNA-substrate interactions129
  • 3 RNase P RNA structure and function137
  • 4 Summary140
  • 5 Concluding remarks141
  • Acknowledgements141
  • References141
  • Chapter 10. Interfering with Gene Function at the RNA Level with Oligozymes - the Development of New145
  • Abstract145
  • 1 Introduction146
  • 2 Oligozymes148
  • 3 Oligozymes based on the hammerhead ribozyme151
  • 4 Choosing a target site on an RNA153
  • 5 Elucidating gene function in vivo155
  • 6 Conclusion157
  • References158
  • Chapter 11. Progress towards Therapeutic Application of SELEX-derived Aptamers161
  • Abstract161
  • 1 Introduction162
  • 2 Design and construction of an oligonucleotide library165
  • 3 Partition167
  • 4 Truncation170
  • 5 Post-SELEX modifications171
  • 6 Aptamer structures171
  • 7 Applications172
  • 8 Conclusion and perspective174
  • Acknowledgements175
  • References175
  • Chapter 12. Catalysis of Organic Reactions by RNA - Strategies for the Selection of Catalytic RNAs179
  • Abstract179
  • 1 Introduction180
  • 2 Selection of catalytic RNA molecules181
  • 3 SELEX with linker-coupled reactants183
  • 4 Future directions187
  • Acknowledgement189
  • References189
  • Conclusions and Opportunities191
  • Appendix: Abstracts of Posters195
  • Index223
  • Color Plate SectionsColor Plate-1
Book details
  • Vendor Elsevier S & T
  • SKU 9780122332104
  • ISBN-13 9780080542553
  • Author Eggleston, D. S.; Prescott, Catherine D.; Pearson, Neil D.
  • Category Medical
  • Subject Genetics

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The Many Faces of RNA is the subject for the eighth SmithKline Beecham Pharmaceuticals Research Symposia. It highlights a rapidly developing area of scientific investigation. The style and format are deliberately designed to promote in-depth presentations and discussions and to facilitate the forging of collaborations between academic and industrial partners.
This symposium focuses on several of the many fundamental, advancing strategies for exploring RNA and its functions. It emphasizes the interplay between biology, chemistry, genomics, and molecular biology which is leading to exciting new insights and avenues of investigation. The book explores RNA as a therapeutic target, RNA as a tool, RNA and its interactions, along with chemical, computational, and structural investigations.