Alternative Splicing in the Postgenomic Era

Hardcover | January 23, 2008

EditorBenjamin J. Blencowe, Brenton R. Graveley

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Alternative Splicing in the Postgenomic Era is the first book that is solely dedicated to the topic of alternative splicing. The book contains chapters by experts in the field that cover nearly all aspects of alternative splicing. The purpose of this book is to provide a single, authoritative source of information on alternative splicing that is accessible to researchers in diverse fields. The book contains information that will familiarize readers that have not previously encountered alternative splicing, but also contains sufficient depth to provide new information to experts in the field.

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Alternative Splicing in the Postgenomic Era is the first book that is solely dedicated to the topic of alternative splicing. The book contains chapters by experts in the field that cover nearly all aspects of alternative splicing. The purpose of this book is to provide a single, authoritative source of information on alternative splici...

Format:HardcoverDimensions:252 pages, 9.25 × 6.1 × 0 inPublished:January 23, 2008Publisher:Springer New YorkLanguage:English

The following ISBNs are associated with this title:

ISBN - 10:0387773738

ISBN - 13:9780387773735

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Table of Contents

CONTENTSFOREWORD......................................................................................................... vPREFACE.............................................................................................................. ixABOUT THE EDITOR S.................................................................................... xiiiPARTICI PANTS.................................................................................................. xv1. Nuclear Organization and Splicing Control..................... 1Maria Carmo-Fonseca and Célia CarvalhoAbstract................................................................................................................................. 1Splicing and the Nucleus...................................................................................................... 1Compartmentalization of Splicing and Splicing Factors.................................................. 3Compartmentalization of Splicing Factors and Splicing Regulation............................... 8Perspectives.......................................................................................................................... 92. Spliceosome Assembly and Composition............................... 14Arianne J. Matlin and Melissa J. MooreAbstract............................................................................................................................... 14Introduction........................................................................................................................ 14Composition and Structure................................................................................................ 14In Vitro Spliceosome Assembly.......................................................................................... 15Product Release and snRNP Recycling............................................................................. 24Interactions at the Ends of Transcripts That PromoteSpliceosome Assembly................................................................................................ 24The Holospliceosome Hypothesis...................................................................................... 24Insights from In Vivo Analysis of Spliceosome Assembly............................................... 25Commitment to Particular Splice Sites............................................................................. 26Proofreading....................................................................................................................... 26Final Comments.................................................................................................................. 283. Relating Alternative Splicing to ProteomeComplexity and Genome Evolution.................................. 36Yi Xing and Christopher LeeAbstract............................................................................................................................... 36Alternative Splicing and Proteomic Complexity.............................................................. 36Alternative Splicing of Protein Domains and Functional Sites...................................... 37Alternative Splicing and Protein Structure...................................................................... 39Alternative Splicing and Genome Evolution.................................................................... 40Alternative Splicing and Amino Acid Mutation Selection Pressure............................... 43Alternative Splicing and RNA Selection Pressure........................................................... 43Connecting RNA Selection Pressure to Real Splicing Regulation.................................. 44Future Challenges............................................................................................................... 454. Complex Alternative Splicing ................................................... 50Jung Woo Park and Brenton R. GraveleyAbstract............................................................................................................................... 50Introduction........................................................................................................................ 50An Overview of Alternative Splicing-From Simple to Complex.................................. 52Mechanisms Used for Mutually Exclusive Splicing in Dscam........................................ 54Conclusions......................................................................................................................... 615. Technologies for the Global Discoveryand Analysis of Alternative Splicing.............................. 64John A. Calarco, Arneet L. Saltzman, Joanna Y. Ip and Benjamin J. BlencoweAbstract............................................................................................................................... 64Introduction........................................................................................................................ 64Microarray-Based Methods for the Large-Scale Discovery and Characterizationof Alternative Splicing Events.................................................................................... 65Applications of Alternative Splicing Microarrays........................................................... 68Non Microarray-Based Methods for the Discovery and Characterizationof Alternative Splicing Events.................................................................................... 75Conclusions......................................................................................................................... 806. Searching for Splicing Motifs.................................................... 85Lawrence A. ChasinAbstract............................................................................................................................... 85Splice Site Sequences Are Necessary but Not Sufficient.................................................. 85The Splice Sites.................................................................................................................... 85The Branch Point................................................................................................................ 86Exon Definition.................................................................................................................... 86Additional Sequence Information Lies within Exons and Introns................................. 88Global Approaches for Defining Sequence Motifs for Splicing...................................... 88Exonic Splicing Enhancers (ESEs) Predicted by Computation...................................... 88Exonic Splicing Silencers (ESSs) Predicted by Computation......................................... 93Exonic Splicing Regulators (ESRs) Predicted by Computation..................................... 93Molecular Selections........................................................................................................... 95Comparison of Computationally Predicted and Functional SELEXSelected Exonic Motifs................................................................................................ 99An Embarrassment of Riches?.......................................................................................... 99The Future......................................................................................................................... 1027. SR Proteins and Related Factors in AlternativeSplicing.............................................................................................. 107Shengrong Lin and Xiang-Dong FuAbstract............................................................................................................................. 107Introduction...................................................................................................................... 107The Role of SR Proteins in Splice Site Selection............................................................ 109SR Proteins Modulate Alternative Splicing in Both Ways............................................ 110How Do SR-Related Splicing Factors Regulate Alternative Splicing?........................ 112Functional Requirement of SR Proteins In Vivo............................................................ 112SR Proteins as Splicing Regulators In Vivo: Why So Few Targets?............................ 113Regulation of SR Splicing Regulators............................................................................. 114SR Protein-Regulated Splicing in Development and Disease....................................... 116Concluding Remarks........................................................................................................ 1168. hnRNP Proteins and Splicing Control.................................... 123Rebeca Martinez-Contreras, Philippe Cloutier, Lulzim Shkreta,Jean-Francois Fisette, Timothée Revil and Benoit ChabotAbstract............................................................................................................................. 123Introduction...................................................................................................................... 123A Brief History of hnrnp Proteins................................................................................. 125hnrnp Proteins, Splicing and Alternative Splicing....................................................... 125Splicing Lessons from the Study of hnrnp Proteins .................................................... 134Concluding Remarks........................................................................................................ 1379. Functional and Mechanistic Insights FromGenome-Wide Studies of Splicing Regulationin the Brain...................................................................................... 148Jernej Ule and Robert B. DarnellAbstract............................................................................................................................. 148Introduction...................................................................................................................... 148At the Intersection between Cancer Cells and Neurons................................................ 148The Three Main Benefits of Splicing Regulation in the Brain...................................... 149Understanding the Nature of Protein-RNA Interactions.............................................. 150An RNA Map for Nova-Dependent Splicing Regulation............................................... 152Relating the RNA Map to Mechanisms of Splicing Regulation.................................... 153Is Combinatorial Splicing Regulation Cooperative or Additive?................................. 154Modular Structure of Coregulated Transcripts............................................................. 154Evolutionary Considerations........................................................................................... 15510. Regulation of Alternative Splicing by Signal Transduction Pathwa ys.......................................................... 161Kristen W. LynchAbstract............................................................................................................................. 161Introduction...................................................................................................................... 161Molecular "hubs" help link the extracellular worldto the splicing machinery........................................................................................ 162Posttranslational modifications of splicing machinery................................................ 163Signal-induced changes in localization of splicing factors....................................... 165Other mechanisms: Altered protein protein interactionsand protein expression............................................................................................. 167Regulation via cross-Talk with signal-Responsive changes in transcription.......... 168Coordinated regulation................................................................................................... 169Achieving specificity in signal-responsiveness of alternative splicing...................... 170Feed-back and feed-forward......................................................................................... 170Summary........................................................................................................................... 17111. Coupling Transcription and Alternative Splicing.... 175Alberto R. KornblihttAbstract............................................................................................................................. 175Introduction...................................................................................................................... 175Promoters Affect Alternative Splicing............................................................................ 177RNAPII CTD and Coupling............................................................................................. 178Factor Recruitment........................................................................................................... 179Recruitment of SRp20, the CTD and Alternative Splicing........................................... 181Transcription Elongation and Alternative Splicing....................................................... 182Slow Polymerases and Alternative Splicing.................................................................... 183Chromatin, Elongation and Alternative Splicing........................................................... 184Coordination Between and Polarity in Multiple Alternative Splicing Events............ 184Conclusions and Perspectives.......................................................................................... 18612. The Coupling of Alternative Splicingand Nonsense-Mediated mRNA Decay................................ 190Liana F. Lareau, Angela N. Brooks, David A.W. Soergel, Qi Mengand Steven E. BrennerAbstract............................................................................................................................. 190Introduction...................................................................................................................... 190Many Alternative Splice Forms Are Targets of NMD................................................... 192Do the Observed PTC+ mRNA Isoforms Evade NMD to ProduceFunctional Protein?.................................................................................................. 195Are the Observed PTC+ mRNA Isoforms a Side Effect of ProductiveAlternative Splicing?................................................................................................ 199Do the Observed PTC+ mRNA Isoforms Represent Missplicingor Cellular Noise?...................................................................................................... 199Are PTC+ mRNA Isoforms Important for the Regulation of Gene Expression?........ 201Constitutive Unproductive Splicing................................................................................ 201Regulated Unproductive Splicing.................................................................................... 202Autoregulatory Unproductive Splicing........................................................................... 203Conservation of Regulated Unproductive Splicing and Translation (RUST)............. 205Why Regulated Unproductive Splicing and Translation?............................................. 20613. Alternative Splicing in Disease............................................... 212James P. Orengo and Thomas A. CooperAbstract............................................................................................................................. 212Introduction...................................................................................................................... 212Tauopathies: Mutations in the MAPT Gene................................................................... 213Myotonic Dystrophy......................................................................................................... 214Facioscapulohumeral Muscular Dystrophy (FSHD)..................................................... 217Cancer and Mis-Regulated Splicing................................................................................ 218Prader-Willi Syndrome (PWS)........................................................................................ 220Conclusions....................................................................................................................... 220Index................................................................................................................. 225