Paddison / Vogt RNA Interference

1. Auflage 2008
ISBN: 978-3-540-75157-1
Verlag: Springer Berlin Heidelberg
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 320, 277 Seiten

Reihe: Current Topics in Microbiology and Immunology

In the last few years the major effect that RNAi has had in invertebrate systems is beginning to take hold in mammalian systems through both single gene knockdown experiments and genome-scale screens. In the next decade, there will no doubt be both notable successes and failures as we attempt to apply this genetic tool to various biological problems. Through the introduction of RNAi, mammalian systems have finally gained admittance to the pantheon of model genetic systems.

Autoren/Hrsg.

Paddison, Patrick J.

Vogt, Peter K.

Inhaltsverzeichnis

1;Contents;5
2;Contributors;7
3;RNA Interference in Mammalian Cell Systems;9
3.1;1 Introduction;9
3.2;2 The RNAi Pathway in Mammals;10
3.3;3 Triggers of RNAi in Mammals;15
3.4;4 Genome-Wide Approaches Using RNAi;17
3.5;5 Off-Target Effects;19
3.6;6 RNAi in the Clinic?;20
3.7;7 Concluding Remarks;21
3.8;References;21
4;RNAi Pathway in C. elegans: The Argonautes and Collaborators;28
4.1;1 A Tiny Worm Shed Light on New Gene Regulation Mechanisms;28
4.2;2 The Argonautes: The Heroes of RNAi Pathways;30
4.3;3 The Argonautes Are Not Alone;36
4.4;4 RNAi Important to Maintain Genome Integrity: A Primitive Immune System in C. elegans?;39
4.5;5 Closing Remarks;40
4.6;References;40
5;Genetics and Biochemistry of RNAi in Drosophila;44
5.1;1 Dicer: RNAi Initiation;46
5.2;2 siRNA: Structure and Its Impact on RNAi;48
5.3;3 Argonaute Proteins: Structure and Function;49
5.4;4 Drosophila AGO Proteins: Unique Features and Crucial Role in RNAi;50
5.5;5 RISC Assembly;52
5.6;6 RISC Assembly Pathway and Target mRNA Cleavage;53
5.7;7 Kinetics of RISC: Consolidating the Structural and Biochemical Data;56
5.8;8 Transcriptional Gene Silencing in Relation to the Polycomb Complex and RNAi;57
5.9;9 RNAi and Transposable Element Expression;59
5.10;10 Cosuppression and I Factor Repression;60
5.11;11 Heterochromatin and P Element Control;61
5.12;12 Hybrid Dysgenesis in D. virilis;62
5.13;13 siRNAs Homologous to Transposable Elements and Viruses;63
5.14;14 Germinal Versus Somatic Silencing;64
5.15;15 Length Maintenance of the Telomeres;66
5.16;16 Transposons Regulate Neighboring Genes by RNAi;67
5.17;17 RNAi Interactions with Heterochromatin, RNA Editing, and DNA Repair;67
5.18;18 Role of RNAi Genes with Chromatin Insulators;72
5.19;19 Stability of the Nucleolus;72
5.20;20 Silencing Interactions with the MSL Complex;72
5.21;21 Concluding Remarks;74
5.22;References;74
6;Role of Dicer in Posttranscriptional RNA Silencing;83
6.1;1 Introduction;83
6.2;2 RNase III Family;84
6.3;3 Dicer Proteins in Different Organisms;86
6.4;4 Proteins Interacting with Dicer;87
6.5;5 Mechanism of dsRNA and Pre-miRNA Processing by Dicer;92
6.6;6 Function of Dicer in the Assembly of Effector Complexes;94
6.7;7 Role of Dicer In Vivo;97
6.8;References;97
7;The Mechanism of RNase III Action: How Dicer Dices;104
7.1;1 Introduction;105
7.2;2 Domain Structure and Function of RNase III Proteins;107
7.3;3 Minimal Functional Core of RNase III Proteins;115
7.4;4 Conclusions;118
7.5;References;119
8;MicroRNA Metabolism in Plants;122
8.1;1 MicroRNA Discovery in Plants;123
8.2;2 MicroRNA Genes in Plants: Organization, Conservation, and Origin;125
8.3;3 MicroRNA Biogenesis in Arabidopsis;126
8.4;4 Regulation of MicroRNA Biogenesis;133
8.5;5 Mode of Action of Plant MicroRNAs;134
8.6;6 Outstanding Questions;135
8.7;References;137
9;Structure-Function Relationships Among RNA-Dependent RNA Polymerases;142
9.1;1 Introduction;143
9.2;2 RdRP Structures;143
9.3;3 Structures of RdRP Complexes;147
9.4;4 Phosphodiester Bond Formation;151
9.5;5 Fidelity;153
9.6;6 RdRPs of RNAi;156
9.7;7 Concluding Remarks;156
9.8;References;157
10;RNAi-Mediated Chromatin Silencing in Fission Yeast;162
10.1;1 Overview;163
10.2;2 The Organisation of Fission Yeast Centromeres;164
10.3;3 Methylated Histone H3 Binds Swi6 to Form Heterochromatin;166
10.4;4 The Role of Heterochromatin at Specific Chromosomal Loci;168
10.5;5 RNAi Components Are Required for Heterochromatin Integrity;170
10.6;6 RNAi Is Dispensable at the Mating-Type Locus and Telomeres;180
10.7;7 Perspectives;182
10.8;References;183
11;A Role for RNAi in Heterochromatin Formation in Drosophila;189
11.1;1 Definition of Heterochromatin;190
11.2;2 Biochemistry of RNAi;194
11.3;3 Links Between RNAi and Heterochromatin;198
11.4;4 Experiments Testing an RNAi Connection in Drosophila;202
11.5;5 Outlook;207
11.6;References;208
12;RNA-Mediated Transcriptional Gene Silencing in Human Cells;214
12.1;1 Introduction;215
12.2;2 Conclusion;224
12.3;References;225
13;RNA Silencing in Mammalian Oocytes and Early Embryos;228
13.1;1 Introduction;229
13.2;2 Mechanisms of RNA Silencing;230
13.3;3 Other dsRNA-Responding Pathways;232
13.4;4 RNA Silencing in Mouse Oocytes and Early Embryos;238
13.5;5 Experimental Use of RNA Silencing in Mouse Oocytes and Early Embryos;245
13.6;6 Conclusions;250
13.7;References;250
14;Identifying Human MicroRNAs;260
14.1;1 Introduction;260
14.2;2 Bioinformatic MicroRNA Prediction: Principles and Challenges;262
14.3;3 A Novel, ‘Integrated’ Approach to MicroRNA Identification;264
14.4;4 On-going Trends in MicroRNA Discovery;268
14.5;References;270
15;Index;273