Looking at Ribozymes

Benoît Masquida is director of research at the French National Center for Scientific Research (CNRS) and carries out his research and teaching activities at the University of Strasbourg, France. He is the author of over 60 publications and is one of France’s leading specialists in ribozymes. Fabrice Leclerc is a research fellow at the CNRS and conducts his research at the Paris-Saclay University, France. He has published numerous articles on RNA catalysis in ribozymes and their role in viroids and in the RNA world.

Foreword vii

Preface xi

Chapter 1 Fundamentals of RNA and Ribozyme Structure 1

1.1 Sequences and secondary structures 2

1.2 RNA folding, tertiary structures and 3D 8

1.2.1 Secondary structures and RNA folding 8

1.2.2 The pseudoknot 12

1.2.3 The loop E 14

1.2.4 The k-turn 16

1.2.5 Tetra-loop receptors 18

1.2.6 The A-minor pattern 20

1.2.7 Comparative analysis of sequences 24

Chapter 2 Ribozymes and the "Central Dogma" of Molecular Biology 29

2.1 The discovery of RNA catalysis and the central dogma of molecular biology 29

2.2 In search of the primordial polymerase 34

Chapter 3 The Discovery of Ribozymes 37

3.1 The discovery of catalysis by autocatalytic introns 38

3.2 The discovery of RNA catalysis of RNase P 42

3.3 The first consequences of these discoveries 46

3.3.1 The ribosome, a long-ignored ribozyme 47

3.3.2 The modified bases 52

3.4 The spliceosome, another ribozyme 55

3.4.1 Nucleolytic ribozymes 56

Chapter 4 Ribozyme Engineering and the RNA World 73

4.1 Classification of ribozymes 75

4.2 Classification of ribozymes according to catalytic mechanism 76

Chapter 5 Structures of Ribozymes 81

5.1 Structures and catalytic mechanisms of ribozymes 81

5.1.1 Hammerhead ribozymes 81

5.1.2 The example of the hairpin ribozyme 87

5.1.3 The example of the glmS ribozyme 89

5.2 An example of catalysis control: lariat-capping ribozyme 91

Chapter 6 Evolution of the Vision of the Catalytic Mechanisms of Ribozymes, the Hammerhead Ribozyme 99

6.1 Chemistry and catalysis: between general acid/base and metal cations 99

6.2 Difficulties in interpreting catalysis data 103

Chapter 7 The Distribution of Ribozymes in Living Organisms and Molecular Adaptations during Evolution 111

7.1 Ubiquitous ribozymes 111

7.2 Selection pressures at work in ribozyme shaping 113

7.3 Ribozymes in cellular processes: from viroids to eukaryotes 117

7.4 Very human ribozymes 123

Conclusion 133

References 135

Index 165