Post-Transcriptional Gene Regulation

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Reflecting the rapid progress in the field, the book presents the current understanding of molecular mechanisms underlying posttranscriptional gene regulation. It focuses on RNA processing mechanisms in eukaryotic cells. With chapters on RNA splicing,
RNA interference, MicroRNA regulation, RNA editing and other biological processes involving RNAs, the book also discusses critical roles of RNA processing in the pathogenesis of a wide range of human diseases. The interdisciplinary importance of the topic makes the title a useful resource for a wide reader group in science, in clinics as well as in the pharmaceutical industry.

Jane Y. Wu is the Charles Louis Mix Professor in the Department of Neurology, the Lurie Cancer Center and the Center for Genetic Medicine at Northwestern University in Chicago, USA as well as a senior consulting investigator at the Chinese Academy of Science, Beijing, China. After obtaining her doctorate from Stanford University and her postdoctoral training at Harvard University, Dr. Wu has been focusing on studying molecular mechanisms controlling gene regulation, in particular, those critical for neural development and neurodegeneration. Her research has significantly advanced our understanding of the fundamental role of RNA processing in biology and in human pathogenesis.


Foreword XI

List of Contributors XIII

1 The Role of Cotranscriptional Recruitment of RNA-Binding Proteins in the Maintenance of Genomic Stability 1
Jennifer A. Aoki and James L. Manley

1.1 Introduction 1

1.2 THO/TREX 2

1.3 Linking Transcription to Export of mRNP 4

1.4 Cotranscriptional R-loop Formation 7

1.5 R-loop-induced Double-Stranded (ds) DNA Breaks 10

1.6 Concluding Remarks 12

References 12

2 Transcription Termination by RNA Polymerase II 19
Minkyu Kim and Stephen Buratowski

2.1 Messenger RNA Gene Termination 19

2.2 Small Nucleolar RNA Gene Termination Pathway 23

2.3 Choice between the Two Termination Pathways 25

2.4 Regulation of Transcription by Termination 27

2.5 Mechanisms of Termination by Other RNA Polymerases 30

2.6 Future Perspectives 31

Acknowledgments 32

References 32

3 Posttranscriptional Gene Regulation by an Editor: ADAR and its Role in RNA Editing 41
Louis Valente, Yukio Kawahara, Boris Zinshteyn, Hisashi Iizasa, and Kazuko Nishikura

3.1 Introduction 41

3.2 The RNA Editing Kinship 44

3.3 The ADAR Gene Family 45

3.4 The Role of RNA in the A-to-I Editing Mechanism 51

3.5 Splice Site Alterations 52

3.6 A-to-I RNA Recoding Modifies Proteins Such As Neurotransmitters 55

3.7 Cellular Effects and in Vivo Phenotypes of ADAR Gene Inactivation 59

3.8 Noncoding RNA and Repetitive Sequences 61

3.9 Effects on the RNA Interference Silencing Pathway 64

3.10 Effects on MicroRNA Processing and Target Selection 66

3.11 RNA Editing Role as an Antiviral Mechanism 67

3.12 Conclusions 68

Acknowledgments 69

References 69

4 Posttranslational Modification of Sm Proteins: Diverse Roles in snRNP Assembly and Germ Line Specification 83
Graydon B. Gonsalvez and A. Gregory Matera

4.1 Introduction 83

4.2 Protein Methylation Flavors and Functions 84

4.3 Sm Proteins Contain sDMA- and aDMA-Modifi ed Arginines 86

4.4 SnRNP Assembly, the Survival Motor Neuron (SMN) Complex, and Spinal Muscular Atrophy (SMA) 87

4.5 PRMT5 and PRMT7 The Sm Protein Methyltransferases 89

4.6 Sm Protein Methylation is Required for sn/RNP Assembly in Mammals 92

4.7 Sm Protein Methylation in Drosophila 94

4.8 Unresolved Questions: Sm Protein Methylation and snRNP Assembly 95

4.9 Conclusion The Evolution of snRNP Assembly 96

4.10 Sm Proteins Are Required for Germ Cell Specification 97

4.11 Dart5, Valois, Sm Proteins, and Tudor Anchoring 100

4.12 Unresolved Questions: Sm Proteins and Germ Cell Specification 101

4.13 The Transcriptional Functions of PRMT5 102

4.14 Arginine Methylation No Longer in the Shadow of Phosphorylation 103

4.15 Sm Proteins Doughnut-Shaped Relics of Our RNA Past 104

References 106

5 Structure, Function, and Biogenesis of Small Nucleolar Ribonucleoprotein Particles 117
Katherine S. Godin and Gabriele ...

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Post-Transcriptional Gene Regulation
RNA Processing in Eukaryotes
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