Translational Control in Health and Disease (eBook)

Front Cover 1
Molecular Biology and Translational Science: Translational Control in Health and Disease 4
Copyright Page 5
Contents 6
Contributes 10
Preface 12
Chapter 1: Molecular Basis of Translational Control 14
I. Introduction 15
II. Initiation Pathway Overview 16
III. Generating a Pool of 40S Ribosomal Subunits 19
IV. Preparing the 40S Subunit for Binding mRNA 21
V. eIF1 and eIF1A 21
VI. Initiator tRNA Recruitment to the 40S Subunit 23
VII. Regulating Ternary Complex Availability 26
VIII. The Role of eIF3 in 43S Complex Formation 27
IX. eIF5 30
X. Controlling mRNA Recruitment to the 40S Subunit 30
XI. Eukaryotic mRNA Characteristics 31
XII. Recruitment of mRNA to the 43S Complex 33
XIII. Ribosomal Scanning and Initiation Codon Recognition 38
XIV. Ribosomal Subunit Joining 41
XV. Regulating the Initiation Pathway 43
XVI. The Mechanism of Translation Elongation 43
XVII. Translation Termination 45
XVIII. Perspectives 47
References 48
Chapter 2: 2 Cell Signaling in Protein Synthesis: Ribosome Biogenesis and Translation Initiation and Elongation 66
I. Introduction 67
II. Translation: The Regulated Steps of Ribosome Biogenesis and Translation Initiation and Elongation 68
III. Signaling Pathways that Control Translation 77
IV. Signaling and Translation Initiation 85
V. Signaling and Elongation 94
VI. Signaling and Ribosome Biogenesis 97
Acknowledgment 105
References 105
Chapter 3: Protein S6 Kinase: From TOP mRNAs to Cell Size 122
I. S6 Kinases 123
II. S6K Substrates and Interactors 129
III. Does S6K Regulate the Translation Efficiency of TOP mRNAs? 134
IV. Physiological Roles of S6K 148
V. Concluding Remarks 153
Acknowledgment 154
References 154
Chapter 4: Regulation of Translation by Stress Granules and Processing Bodies 168
I. Introduction 169
II. Early History of Stress Granules 170
III. Stress Granules-Basic Attributes 178
IV. Processing Bodies/EGP Bodies/SGs in Yeast 180
V. Metazoan PBs Versus GWBs 182
VI. SG Assembly-Mechanisms and Model 183
VII. Functions and Consequences of SG/PB Assembly 185
VIII. SG/PB Dynamics 187
IX. SGs and PBs in Disease 188
X. Conclusions 192
References 192
Chapter 5: MicroRNA-Mediated Gene Silencing 200
I. Introduction 201
II. Biogenesis of MicroRNAs 203
III. Mechanisms of MicroRNA-Mediated Regulation 206
IV. Subversion of Liver-Specific MicroRNA miR-122 by HCV 212
V. Antagomir Approaches to Study MicroRNA Targets 215
VI Concluding Remarks 217
References 218
Chapter 6: Translational Control During Early Development 224
I. Introduction 225
II. Essential Background 226
III. Translational Control Mechanisms that Pattern the Early Drosophila Embryo 230
IV. Cytoplasmic Regulation of Polyadenylation: A Widespread Mechanism of Translational Control Underlying Cellular Asymmetries 239
V. Polar Granules, P Granules, and Related Germline-Specific Organelles as Sites of Specialized Translation 243
VI. Translational Regulation of Maternal mRNAs Outside P Granules in C. elegans 246
VII. Translational Control of Localized mRNAs in the Xenopus Oocyte 247
VIII. Links Between Embryonic Translational Regulators and Human Disease 249
IX. Concluding Thoughts 251
Acknowledgment 252
References 252
Chapter 7: The Regulation of Protein Synthesis in Cancer 268
I. Historical Evidence for the Role of Protein Synthesis in Cancer 269
II. Translation Initiation 269
III. The Role of eIF3 in Cancer Development 274
IV. Role of eIF2 in Cancer Development and Progression 275
V. Ribosome Biogenesis in Cancer Development 277
VI. Translational Regulation by mRNA 5prime- and 3prime-UTRs 280
VII. Signal Transduction Control of Translation in Cancer 286
VIII. Concluding Thoughts 293
Acknowledgment 294
References 294
Chapter 8: Translational Regulatory Mechanisms in Synaptic Plasticity and Memory Storage 306
I. Synaptic Plasticity Control by eIF2 307
II. GCN2-Mediated eIF2alpha Phosphorylation in Long-Lasting Synaptic Plasticity and LTM Consolidation 308
III. eIF2alpha Phosphorylation and Alzheimer's Disease 310
IV. Regulation by mTOR 311
V. Regulation of Protein Synthesis-Dependent Synaptic Plasticity and Memory Consolidation by 4E-BP2 and S6K1 and S6K2 311
VI. Altered mTOR Signaling and Autism Spectrum Disorders 312
VII. FMRP and Long-Lasting Hippocampal Synaptic Plasticity 313
VIII. Translational Control by FMRP 314
IX. The Exon Junction Complex and the Regulation of Synaptic Strength 316
X. CPEB-Regulated Molecular Circuitry 317
XI. Perspective 319
References 320
Chapter 9: Viral Strategies to Subvert the Mammalian Translation Machinery 326
I. Introduction 327
II. Viral Modification of Host Translation Machinery 328
III. Novel Mechanisms that Permit the Synthesis of Viral Proteins 349
IV. Mechanisms to Overcome Host-Mediated Translational Shut Down Caused by Phosphorylation of eIF2 360
V. General Conclusions 365
Acknowledgment 368
References 368
Chapter 10: RNA Aptamers to Translational Components 382
I. Introduction 383
II. Aptamers to Translational Components 385
III. Other Tools for the Regulation of Translation 397
IV. Summary and Perspectives 399
Acknowledgment 400
References 400
Index 410
Color Plate 422