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BL
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| Record Number
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866008
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| Title & Author
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RNA Metabolism in Neurodegenerative Diseases /\ Rita Sattler, Christopher J. Donnelly, editors.
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| Publication Statement
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Cham, Switzerland :: Springer,, [2018]
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, ©2018
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| Series Statement
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Advances in neurobiology ;; volume 20
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| Page. NO
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1 online resource
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| ISBN
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3030078329
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: 331989689X
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: 3319896903
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: 9783030078324
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: 9783319896892
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: 9783319896908
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3319896881
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9783319896885
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| Bibliographies/Indexes
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Includes bibliographical references and index.
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| Contents
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Intro; Preface; Contents; Contributors; About the Editors; Abbreviations; Chapter 1: An Epigenetic Spin to ALS and FTD; 1.1 Introduction; 1.2 Epigenetic Mechanisms; 1.2.1 Nuclear DNA Methylation; 1.2.2 Nuclear DNA Demethylation; 1.2.3 Mitochondrial DNA Methylation; 1.2.4 RNA Methylation; 1.2.5 RNA-Mediated Regulation; 1.2.6 Histone Modifications; 1.3 Epigenetic Changes in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD); 1.3.1 ALS/FTD Epigenetic Studies; 1.3.1.1 Nuclear DNA methylation/demethylation; 1.3.1.2 RNA-mediated regulation through miRNAs.
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1.3.2 C9orf72 Epigenetic Studies1.3.3 Potential Drivers of Epigenetic Changes; 1.3.4 Therapeutic Potential; References; Chapter 2: Mechanism of Splicing Regulation of Spinal Muscular Atrophy Genes; 2.1 Introduction; 2.2 Organization of Human SMN Genes; 2.3 Regulation of SMN Exon 7 Splicing; 2.3.1 In Vivo Selection of Exon 7; 2.3.2 Effect of Terminal Stem Loop 2; 2.3.3 Effect of Intronic Splicing Silencer N1; 2.3.4 Effect of U-Rich Clusters Within Intron 7; 2.3.5 Effect of Long-Distance Interactions Within Intron 7; 2.3.6 Extension of Exon 7 by the Activation of a Cryptic 5'ss.
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2.3.7 Role of cis-Elements Within Intron 62.4 Exonization of an Intronic Alu-Element; 2.5 Alternative Splicing of Other SMN Exons; 2.6 Effect of Transcription on Splicing of Various SMN Exons; 2.7 Conclusions; References; Chapter 3: RNA Editing Deficiency in Neurodegeneration; 3.1 Introduction: RNA Editing Overview; 3.1.1 Major CNS RNA Editing Targets; 3.1.1.1 AMPA Receptors; 3.1.1.2 Serotonin Receptors; 3.1.1.3 Voltage Gated Potassium Channels; 3.2 RNA Editing Deficits in Neurodegeneration; 3.2.1 RNA Editing in Chronic Neurodegenerative Diseases; 3.2.2 RNA Editing in Acute Neurodegeneration.
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3.3 A ₂!I RNA Editing Dysfunction in Psychiatric Diseases3.4 Brain Cancer; 3.5 Conclusions; References; Chapter 4: RNA Nucleocytoplasmic Transport Defects in Neurodegenerative Diseases; 4.1 Introduction; 4.2 Export of RNA from the Nucleus; 4.2.1 Nuclear Pores Regulate Transport Between the Nucleus and the Cytoplasm; 4.2.2 Exportin-Mediated Export of RNA; 4.2.3 NXF1 Is the Primary Transporter of mRNA; 4.3 Alterations in RNA Export and in Proteins Required for RNA Export Have Been Identified in Neurodegenerative Diseases; 4.3.1 Nuclear Pore Alterations in Neurodegenerative Diseases.
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4.3.2 Alterations in the RanGTPase Gradient Have Been Identified in Neurodegenerative Diseases4.3.3 Nuclear mRNA Retention in Neurodegenerative Diseases; 4.4 Conclusions; References; Chapter 5: RNA Degradation in Neurodegenerative Disease; 5.1 Mechanisms to Maintain RNA Stability; 5.1.1 Polyadenylation; 5.1.2 Methylguanine Cap; 5.1.3 Secondary Structure; 5.1.4 Stress Granules; 5.2 Mechanisms of RNA Decay; 5.2.1 RNA Degradation Machinery; 5.2.2 Nonsense-Mediated Decay; 5.2.2.1 Alternative Exon Inclusion and Exclusion; 5.2.2.2 Upstream Open Reading Frames; 5.2.3 Nonstop Decay; 5.2.4 No-Go Decay.
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| Abstract
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"It has become evident over the last years that abnormalities in RNA processing play a fundamental part in the pathogenesis of neurodegenerative diseases. Cellular viability depends on proper regulation of RNA metabolism and subsequent protein synthesis, which requires the interplay of many processes including transcription, pre---mRNA splicing, mRNA editing as well as mRNA stability, transport and translation. Dysfunction in any of these processes, often caused by mutations in the coding and non--- coding RNAs, can be very destructive to the cellular environment and consequently impair neural viability. The result of this RNA toxicity can lead to a toxic gain of function or a loss of function, depending on the nature of the mutation. For example, in repeat expansion disorders, such as the newly discovered hexanucleotide repeat expansion in theC9orf72 gene found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), a toxic gain of function leads to the formation of RNA foci and the sequestration of RNA binding proteins (RBPs). This in return leads to a loss of function of those RBPs, which is hypothesized to play a significant part in the disease progression of ALS and FTD. Other toxicities arising from repeat expansions are the formation of RNA foci, bi---directional transcription and production of repeat associated non---ATG (RAN) translation products. This book will touch upon most of these disease mechanisms triggered by aberrant RNA metabolism and will therefore provide a broad perspective of the role of RNA processing and its dysfunction in a variety of neurodegenerative disorders, including ALS, FTD, Alzheimer's disease, Huntington's disease, spinal muscular atrophy, myotonic dystrophy and ataxias. The proposed authors are leading scientists in the field and are expected to not only discuss their own work, but to be inclusive of historic as well as late breaking discoveries. The compiled chapters will therefore provide a unique collection of novel studies and hypotheses aimed to describe the consequences of altered RNA processing events and its newest molecular players and pathways."--
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| Subject
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Nervous system-- Degeneration.
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RNA-- Metabolism.
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HEALTH FITNESS-- Diseases-- General.
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MEDICAL-- Clinical Medicine.
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MEDICAL-- Diseases.
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MEDICAL-- Evidence-Based Medicine.
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MEDICAL-- Internal Medicine.
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| Subject
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Nervous system-- Degeneration.
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| Subject
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RNA-- Metabolism.
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| Dewey Classification
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616.8047
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| LC Classification
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RC365
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| Added Entry
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Donnelly, Christopher J.
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Sattler, Rita
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