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Tables of Contents for Regulation of Alternative Splicing
Chapter/Section Title
Page #
Page Count
Prediction and Statistical Analysis of Alternatively Spliced Exons
T.A. Thanaraj
S. Stamm
Overview
1
1
Mechanism of Splicing
2
3
General Splicing Mechanism
2
1
Exon Definition
2
1
Splice-Site Recognition Is Influenced by the Relative Concentration of Regulatory Proteins
3
2
Properties of Alternative Spliced Exons
5
13
Several Types of Splicing
5
1
Types of Exons
6
1
Regulatory Elements
7
1
5' Splice Site
8
1
3' Splice Site
9
1
Branch Point
10
1
Overall Splice Site Quality
10
1
Exonic Elements
10
6
Length of Alternative Exons
16
2
A Major Function of Alternative Exons Are the Introduction of Premature Stop Codons
18
1
Bioinformatics Resources to Identify Alternative Exons
18
8
Detection of Alternative Splice Events Using Sequence Comparison
19
1
Computer Programs for Detecting Alternative Splicing
19
3
Finding Alternative Exons from Known Gene Structures
22
1
Finding Alternative Splice Events in Genome Regions of Unknown Gene Structures
22
2
Limitations, Problems and Accuracy of Predicting Alternative Splicing Events
24
1
Ad initio Prediction of Alternative Exons
25
1
Overview of Available Databases and Programs
26
7
References
27
6
Multiple Roles of the SR Protein Family in Splicing Regulation
J.R. Sanford
D. Longman
J.F. Caceres
Introduction
33
1
Spliceosome Assembly
34
2
The Serine and Arginine-Rich Family of Proteins
36
2
The Many Roles of Serine and Arginine-Rich Proteins in Constitutive Splicing
38
1
Actions of Serine and Arginine-Rich Proteins and hnRNP A/B Proteins in Splice Site Selection
39
3
Serine and Arginine-Rich Modular Domains
42
2
RNA Binding Activities
42
1
The RS Domain
43
1
Role of the Modular Domains of Serine and Arginine-Rich Proteins in Constitutive and Alternative Splicing
44
4
Constitutive Splicing Activities
44
1
Alternative Splicing Activities
45
3
Functional Redundancy of Serine and Arginine-Rich Proteins
48
1
Role of Transcription in Alternative Splicing
49
1
Alternative Splicing and Signal Transduction
49
2
Conclusions
51
8
References
52
7
Heterogeneous Nuclear Ribonucleoprotein Particle A/B Proteins and the Control of Alternative Splicing of the Mammalian Heterogeneous Nuclear Ribonucleoprotein Particle A1 Pre-mRNA
B. Chabot
C. LeBel
S. Hutchison
F.H. Nasim
M.J. Simard
Heterogeneous Nuclear Ribonucleoprotein Particle Proteins and Splicing
59
4
HnRNP Proteins
59
1
HnRNP Proteins and Generic Splicing
60
1
HnRNP Proteins and Alternative Splicing
61
1
The Function of Core hnRNP A/B Proteins in Splice Site Selection
62
1
The hnRNP A1 Alternative Splicing Unit
63
15
High-Affinity Binding Sites for hnRNP A/B Proteins Contribute to Exon Skipping
64
2
A Model to Explain how A1 Modulates 5' Splice Site Selection
66
4
Repression of a Looped Out 5' Splice Site
70
1
Activation of the External Pair of Splice Sites
71
1
Functional Redundancy Between Core hnRNP A/B Protein Members
72
1
The Looping Model and Other hnRNP Proteins
73
1
RNA Duplex Formation and 5' Splice Site Selection
74
1
Elements Controlling 3' Splice Site Selection
75
3
Conclusions
78
11
A Role for the hnRNP A1 Protein in Alternative and Constitutive Splicing
78
3
Several Elements Control the Alternative Splicing of Exon 7B
81
1
References
82
7
Phosphorylation-Dependent Control of the Pre-mRNA Splicing Machinery
J. Soret
J. Tazi
Introduction
89
1
Spliceosome Assembly and Pre-mRNA Splicing
90
3
Dynamic Assembly of the Spliceosome
90
1
Dissecting the Requirement for ATP in Pre-mRNA Splicing
91
2
Phosphorylation of Serine/Arginine-Rich Prote in Splicing Factors
93
2
Regulation of Splicing
93
2
Regulation of Cellular Localization
95
1
Serine/Arginine-Rich Protein Kinases
95
9
SRPK Protein Family
95
2
Clk/Sty Kinase Family
97
3
DNA Topoisomerase I
100
4
Phosphorylation of SR-Like Proteins
104
1
Phosphorylation of hnRNP Proteins
105
4
HnRNP A1
105
2
SF1/BBP, Member of the hnRNP-K Family
107
1
HnRNP C
108
1
Phosphorylation of snRNP Components
109
3
The U1 snRNP-Specific Protein 70K
109
2
The U2 snRNP Protein 155K
111
1
The U4/U5/U6 Associated Proteins
112
1
Concluding Remarks
112
15
References
113
14
Splicing Regulation in Drosophila Sex Determination
P. Forch
J. Valcarcel
Introduction
127
1
Establishment and Maintenance of Sexual Identity
128
2
Sex-Lethal Proteins
130
3
Somatic Sexual Differentiation
133
5
Regulation of transformer
133
3
Regulation of doublesex
136
2
Dosage Compensation
138
2
Sexual Behavior
140
1
Fruitless
140
1
Transformer-2 Autoregulation
141
1
Sex-lethal Autoregulation
142
2
Perspectives
144
9
References
144
9
Alternative Pre-mRNA Splicing and Regulation of Programmed Cell Death
J.Y. Wu
H. Tang
N. Havlioglu
Introduction
153
2
Alternative Splicing of PCD Genes
155
11
Death Signals and Death Receptors: Modulation of Both Ligands and Receptors by Alternative Splicing
156
3
Cell Death Signal Transducing Adaptor Genes: Multiple Isoforms with Distinct Activities
159
4
Caspase Family and Caspase Regulatory Proteins: Fine-Tuned Dosage Control
163
3
Caspase-Activated DNase and Inhibitor of Caspase-Activated DNase
166
1
The Role of Alternative Splicing in Regulation of Functional Activities of PCD Genes
166
5
Regulation of Subcellular Localization
167
2
Modulation of Functional Activities
169
1
Influencing mRNA Stability or Translational Regulation
170
1
Molecular Mechanism Underlying the Regulation of Alternative Splicing of PCD Genes
171
6
Splicing Machinery and Alternative Splicing Regulators
171
1
Splicing Signals and cis-Regulatory Elements for Splicing
172
3
Changes in Expression of Splicing Regulators During Cell Death
175
1
Tissue- or Cell-Type Specificity of Alternative Splicing of Programmed Cell Death Genes
176
1
Conclusion
177
10
References
178
9
Alternative Pre-mRNA Splicing and Neuronal Function
D.L. Black
P.J. Grabowski
Introduction
187
1
Cell-Cell Interactions and Neuronal Differentiation
188
2
Neurotransmission: Splicing Control of Neurotransmitter Receptors and Ion Channels
190
3
AMPA Receptors
190
1
NMDA R1 Receptor
191
1
Dopamine Receptors
192
1
GABA Receptors
192
1
Voltage-Dependent Potassium and Sodium Channels
193
2
Calcium Channels
194
1
Calcium and Voltage-Activated Potassium Channels
194
1
Mechanisms of Alternative Splicing Control
195
11
Splicing Repression
197
3
Splicing Enhancement
200
2
Neuronal RNA Binding Proteins
202
1
Splicing and Cell Excitation
203
1
Alternative Splicing and Neurological Disease
204
2
Conclusions
206
11
References
206
11
Modulation of Alternative Splicing by Antisense Oligonucleotides
P. Sazani
R. Kole
Introduction
217
1
Manipulation of Splicing by Antisense Oligonucleotides
218
6
RNA Repair in Genetic Disorders
218
1
β-Globin
218
1
Cystic Fibrosis Transmembrane Conductance Regulator
219
2
Dystrophin
221
1
Tau
222
1
Modification of Splicing in Cancer
222
1
Bcl-x
222
1
IL-5R
223
1
C-myc
224
1
Oligonucleotides as Probes for Splicing Mechanisms
224
4
Identification of Splicing Elements
225
1
Splice Site Accessibility
226
2
Splicing Assay for Antisense Activity of Oligonucleotides
228
4
Synthetic Antisense Oligonucleotides
228
1
2'-Modifications of Ribose
228
2
Backbone Modifications
230
1
Base Modifications
231
1
Splicing Assay for Antisense Activity of Synthetic Oligonucleotides
231
1
Site of Action of Antisense Oligonucleotides
232
2
The Nucleus vs. Cytoplasm
232
2
Conclusion
234
7
References
235
6
Subject Index
241