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E-raamat: Post Transcriptional Regulation by STAR Proteins: Control of RNA Metabolism in Development and Disease

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This book aims to bring to the forefront a field that has been developing since the late 1990s called the STAR pathway for Signal Transduction and Activation of RNA. It is a signaling pathway that targets RNA directly; in contrast to the canonical signal-kinase cascade-transcription factor-DNA-RNA. It is proposed to allow quick responses to environment changes such as those necessary in many biological phenomenona such as the nervous system, and during development. The pathway is diagramed in Chapter 1, Figure1. This chapter is a historical introduction and general review with some new data on theoretical miRNAs binding sites and STAR mRNAs. In Chapter 2, Feng and Banks address the accumulating evidence that the RNA-binding activity and the homeostasis of downstream mRNA targets of STAR proteins can be regulated by phosphorylation in response to various extracellular signals. Then Ryder and Massi review the available information on the structure of the RNA binding STAR domain and provides insights into how these proteins discriminate between different RNA targets. Next Claudio Sette offers an overview of the post-translational modifications of STAR proteins and their effects on biological functions, followed by two chapters dedicated to in depth review of STAR function in spermatogenesis and in mammalian embryonic development. Chapters 7 and 8 discuss what can be learned from STAR proteins in non-mammalian species; in Drosophila and Gld-1 and Asd-2 in C. elegans. Next Rymond discusses the actual mech- ics of splicing with mammalian SF1.
1 Star Trek: An Introduction to Star Family Proteins and Review of Quaking (QKI)
1(24)
Karen Artzt
Jiang I. Wu
Abstract
1(1)
History of the STAR Family
1(3)
The Domain Structure and Alternate Splicing of STAR Proteins
4(1)
STAR Proteins Have a Multitude of Developmental Functions
5(1)
Diverse Molecular Functions of STAR Proteins in RNA Processing
5(1)
QK Expression in the Adult Nervous System and Disease
6(2)
QK 3' UTR Conservation and a High Theoretical Number of miRNA Binding Sites
8(3)
Discussion and Conclusion
11(10)
Future Applications, New Research, Anticipated Developments
21(4)
2 The Star Family Member: QKI and Cell Signaling
25(12)
Yue Feng
Andrew Bankston
Abstract
25(1)
Introduction
25(1)
QKI Is Essential for Embryonic and Postnatal Development
26(1)
Phosphorylation of QKI Isoforms by Src-PTKS Regulates the Cellular Fate of QKI mRNA Targets at Multiple Post-Transcriptional Steps
27(3)
Numerous Extracellular Signals Can Be Linked to the Src-PTK-QKI Pathway
30(2)
Potential Role of QKI And Src-PTK Signaling in Tumorigenesis and Congnitive Diseases
32(1)
Conclusion
33(4)
3 Insights Into the Structural Basis of RNA Recognition by Star Domain Proteins
37(17)
Sean P. Ryder
Francesca Massi
Abstract
37(1)
Introduction
37(2)
The STAR Domain
39(1)
RNA Recognition by STAR Proteins
39(4)
Star Domain Structure
43(7)
Conclusion
50(1)
Note Added in Proof
50(4)
4 Post-Translational Regulation of Star Proteins and Effects on Their Biological Functions
54(13)
Claudio Sette
Abstract
54(1)
Introduction
55(1)
Sam68: A Brief Overview
55(2)
Regulation of Sam68 Functions by Tyrosine Phosphorylation
57(2)
Regulation of Sam68 Functions by Serine/Threonine Phosphorylation
59(1)
Regulation of Sam68 Functions by Methylation
60(1)
Regulation of Sam68 Functions by Acetylation and Sumoylation
61(1)
Post-Translational Modifications of SLM-1 and SLM-2
61(1)
Post-Translational Modifications of the QKI Proteins
62(1)
Post-Translational Modifications of SF1
63(1)
Conclusion
63(4)
5 Expression and Functions of The Star Proteins Sam68 And T-Star in Mammalian Spermatogenesis
67(15)
Ingrid Ehrmann
David J. Elliott
Abstract
67(1)
Gene Expression Control in Spermatogenesis
67(3)
Expression of STAR Proteins during Spermatogenesis
70(1)
Protein Structure and Modifications
70(6)
Mouse Knockout Models Define the Roles of STAR Proteins in Testis Function
76(1)
The STAR Protein Sam68 Is Involved in Translational Control in Spermatogenesis
76(1)
STAR Proteins Might Play Roles in Pre-mRNA Splicing control in Spermatogenesis
77(1)
Other Potential Roles of STAR Proteins in Spermatogenesis
78(1)
Conclusion
78(4)
6 The Role of Quaking In Mammalian Embryonic Development
82(11)
Monica J. Justice
Karen K. Hirschi
Abstract
82(1)
Introduction
83(1)
Quaking Is Required for the Formation of Embryonic Vasculature
84(1)
QKI5 Regulates QKI6 and QKI7 in Visceral Endoderm
84(1)
Molecular Basis of Blood Vessel Formation
85(1)
Quaking Is Required for Visceral Endoderm Differentiated Function
86(2)
Other Possible Roles for Quaking in Cardiovascular Development
88(1)
The Evolving Roles of Quaking Function
88(1)
Conclusion
89(4)
7 Drosophila Star Proteins: What Can be Learned From Flies?
93(13)
Talila Volk
Abstract
93(1)
STAR Proteins in Drosophila
93(1)
HOW Regulates Differentiation of Diverse Tissues
94(6)
HOW and Kep 1 Regulate Cell Division and Apoptosis in Drosophila
100(3)
Conclusion
103(1)
Note Added in Proof
104(2)
8 C. Elegans Star Proteins, GLD-1 and ASD-2, Regulate Specific RNA Targets to Control Development
106(17)
Min-Ho Lee
Tim Schedl
Abstract
106(1)
Multiple Functions of GLD-1 in Germline Development
106(3)
GLD-1 Molecular Analysis
109(1)
mRNA Targets: GLD-1 Is a Translational Repressor
110(4)
mRNA Targets: Further Insights into GLD-1 Function in Germline Development
114(1)
mRNA Targets: Towards Defining the GLD-1 RNA Binding Motif and Mechanism of Translational Repression
115(2)
How Is GLD-1 Expression Regulated?
117(2)
ASD-2, Another C. elegans STAR Protein, Functions in Alternative Splicing
119(1)
Conclusion
119(4)
9 The Branchpoint Binding Protein: In and Out of the Spliceosome Cycle
123(19)
Brian C. Rymond
Abstract
123(1)
BBP and SF1 Are Site-Specific RNA Binding Proteins
124(2)
A BBP-Mud2 Heterodimer Functions in Branchpoint Recognition
126(1)
BBP-MUD2 and the Dynamics of Early Spliceosome Assembly
127(3)
Co-Transcriptional Pre-mRNA Splicing
130(1)
But Is BBP Really an Essential Splicing Factor?
131(1)
BBP Is Needed for the Nuclear Retention of Unprocessed Pre-mRNA
131(2)
Uncoupling Pre-mRNA Splicing from the Synthesis of Functional mRNA
133(1)
Does BBP Have a Cytoplasmic Function?
133(1)
Does BBP Regulate the Fate of Intronless RNA?
134(1)
Conclusion
135(7)
10 Reaching for the STARS: Linking RNA Binding Proteins to Diseases
142(17)
Stephane Richard
Abstract
142(1)
Sam68: Its Discovery and Nomenclature
142(1)
The KH Domain
143(2)
Sam68 RNA Targets
145(1)
Sam68 Cellular Localization
146(1)
Sam68 Signaling Motifs
147(1)
Arginine Methylation
148(1)
STAR Protein Mouse Models
149(1)
Sam68 Null Mice
149(1)
QKI Mouse Models
150(1)
STAR Proteins and Human Diseases
151(1)
Osteoporosis
151(1)
Schizophrenia
152(1)
Ataxia
152(1)
Cancer
152(1)
Conclusion
153(6)
Index 159
Talila Volk is an associate professor in the field of Developmental Biology and the incumbent of the Sir Ernest B. Chain Professional Chair. Her major research interest is in tissue morphogenesis and organogenesis during embryonic development. She has been studying the function and activity of the STAR family member Held Out Wing (HOW) in the fruit fly Drosophila since 1999. She served as the chair for the Society of Developmental Biology in Israel (ISDB). Dr. Volk has gained her BSc from TelAviv University, and her MSc and PhD degrees from the Weizmann Institute of Science, Rehovot, Israel.

Karen Artzt is an Ashbel Smith Professor Emeritus at the University of Texas at Austin where she directed a research laboratory for 20 years. There she was a member of the Section of Molecular Genetics and Microbiology. Prior to that she was an associate Member of the Memorial Sloan Kettering Cancer Center in New York. Her main research interests include developmental genetics with an emphasis on cancer biology. In collaboration with Tom Ebersole she identified and cloned the mouse gene quaking that was one of the founding members of the STAR family. Dr. Artzt received her academic degrees from Cornell university; a BA from the Ithaca campus and a PhD from the Medical College School of Graduate Sciences in New York City. In 1972 she spent a year as a postdoctoral fellow at the Pasteur Institute in Paris under the direction of the Nobel Prize winner, Francois Jacob.