Alternative Splicing in Brain Function

Alternative Splicing in Brain Function PDF Author: Kif Liakath-Ali
Publisher: Frontiers Media SA
ISBN: 2832540732
Category : Science
Languages : en
Pages : 171

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Book Description
Functional and structural intricacies of biological systems emerge from the complex nature of the genome. A key aspect of genome complexity can be attributed to the process of alternative splicing of precursor mRNA (or pre-mRNA), during which introns are removed and exons are selectively spliced together. This highly regulated process generates different mature mRNA transcripts from a single gene and is widespread throughout the eukaryotic evolution. The majority of the genes expressed in the mammalian central nervous system undergo extensive alternative splicing. Some genes can generate more than a thousand isoforms resulting in diverse proteoforms that can differ in their function, binding preference, catalytic activity, and localization. Perturbation in alternative splicing has been linked to many neurological disorders. Despite its significance, we still lack a comprehensive understanding of its role in neuronal function. Recent studies suggest that alternative splicing is a regulator of tissue identity and development. This is particularly relevant to the brain where developmental regulation and heterogenous cell population play a crucial role in shaping its function. For a long time, technological limitations in detecting and measuring alternatively spliced transcripts hindered the progress in understanding the biology of alternative splicing. Recent advances in long-read and native mRNA sequencing and robust computational tools allow us to capture and quantify in their full-length form. Public transcriptomics datasets can be utilized for the meta-analysis of alternative splicing landscapes of various experimental conditions and disease samples. In addition, protein isoform detection complements mRNA isoform levels. Given its biological significance and recent advances, the objective of this Research Topic is to assemble current knowledge, views, and challenges in the studies of alternative splicing in brain function.

Alternative Splicing in Brain Function

Alternative Splicing in Brain Function PDF Author: Kif Liakath-Ali
Publisher: Frontiers Media SA
ISBN: 2832540732
Category : Science
Languages : en
Pages : 171

Get Book Here

Book Description
Functional and structural intricacies of biological systems emerge from the complex nature of the genome. A key aspect of genome complexity can be attributed to the process of alternative splicing of precursor mRNA (or pre-mRNA), during which introns are removed and exons are selectively spliced together. This highly regulated process generates different mature mRNA transcripts from a single gene and is widespread throughout the eukaryotic evolution. The majority of the genes expressed in the mammalian central nervous system undergo extensive alternative splicing. Some genes can generate more than a thousand isoforms resulting in diverse proteoforms that can differ in their function, binding preference, catalytic activity, and localization. Perturbation in alternative splicing has been linked to many neurological disorders. Despite its significance, we still lack a comprehensive understanding of its role in neuronal function. Recent studies suggest that alternative splicing is a regulator of tissue identity and development. This is particularly relevant to the brain where developmental regulation and heterogenous cell population play a crucial role in shaping its function. For a long time, technological limitations in detecting and measuring alternatively spliced transcripts hindered the progress in understanding the biology of alternative splicing. Recent advances in long-read and native mRNA sequencing and robust computational tools allow us to capture and quantify in their full-length form. Public transcriptomics datasets can be utilized for the meta-analysis of alternative splicing landscapes of various experimental conditions and disease samples. In addition, protein isoform detection complements mRNA isoform levels. Given its biological significance and recent advances, the objective of this Research Topic is to assemble current knowledge, views, and challenges in the studies of alternative splicing in brain function.

Alzheimer’s and Parkinson’s Diseases

Alzheimer’s and Parkinson’s Diseases PDF Author: Israel Hanin
Publisher: Springer Science & Business Media
ISBN: 1475791453
Category : Medical
Languages : en
Pages : 690

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Book Description
This book represents the third in a series of International Conferences related to Alzheimer's (AD) and Parkinson's (PD) diseases. The first one took place in Eilat, Israel, in 1985; and the second one in Kyoto, Japan, in 1989. This book contains the full text of oral and poster presentations from the Third International Conference on Alzheimer's and Parkinson's Diseases: Recent Developments, held in Chicago, Illinois, U.S.A. on November 1-6, 1993. The Chicago Conference was attended by 270 participants. The Scientific Program was divided into nine oral sessions, a keynote presentation, and a poster session. The conference culminated in a Round Table Discussion involving all of the participants in the conference. The four and one-half day meeting served as an excellent medium for surveying the current status of clinical and preclinical developments in AD and PD. There were 59 oral presentations and 93 posters. This book incorporates a majority of both.

Alternative Splicing and Disease

Alternative Splicing and Disease PDF Author: Philippe Jeanteur
Publisher: Springer Science & Business Media
ISBN: 3540344497
Category : Science
Languages : en
Pages : 265

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Book Description
Splicing of primary RNA transcript is a quasi-systematic step of gene expression in higher organisms. This is the first book to highlight the medical implications, i.e. diseases, caused by alternative splicing. Alternative splicing not only vastly increases protein diversity but also offers numerous opportunities for aberrant splicing events with pathological consequences. The book also outlines possible targets for therapy.

Functional and Mechanistic Analyses of Neural-regulated Alternative Splicing

Functional and Mechanistic Analyses of Neural-regulated Alternative Splicing PDF Author: Bushra Nadia Raj
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Book Description


Regulation of Alternative Splicing

Regulation of Alternative Splicing PDF Author: Philippe Jeanteur
Publisher: Springer Science & Business Media
ISBN: 9783540438335
Category : Science
Languages : en
Pages : 272

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Book Description
The discovery in 1977 that genes are split into exons and introns has done away with the one gene - one protein dogma. Indeed, the removal of introns from the primary RNA transcript is not necessarily straightforward since there may be optional pathways leading to different messenger RNAs and consequently to different proteins. Examples of such an alternative splicing mechanism cover all fields of biology. Moreover, there are plenty of occurrences where deviant splicing can have pathological effects. Despite the high number of specific cases of alternative splicing, it was not until recently that the generality and extent of this phenomenon was fully appreciated. A superficial reading of the preliminary sequence of the human genome published in 2001 led to the surprising, and even deceiving to many scientists, low number of genes (around 32,000) which contrasted with the much higher figure around 150,000 which was previously envisioned. Attempts to make a global assessment of the use of alternative splicing are recent and rely essentially on the comparison of genomic mRNA and EST sequences as reviewed by Thanaraj and Stamm in the first chapter of this volume. Most recent estimates suggest that 40-60% of human genes might be alternatively spliced, as opposed to about 22% for C. elegans.

Visualizing RNA Dynamics in the Cell

Visualizing RNA Dynamics in the Cell PDF Author:
Publisher: Academic Press
ISBN: 0128024887
Category : Science
Languages : en
Pages : 412

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Book Description
Methods in Enzymology: Visualizing RNA Dynamics in the Cell continues the legacy of this premier serial with quality chapters authored by leaders in the field. This volume covers research methods visualizing RNA dynamics in the cell, and includes sections on such topics as identification of RNA cis-regulatory sequences, IRAS, IMAGEtags, MERFISH, plant RNA labeling using MS2, and visualization of 5S dynamics in live cells using photostable corn probe. Continues the legacy of this premier serial with quality chapters authored by leaders in the field Covers research methods in visualizing RNA dynamics in the cell Contains sections on such topics as identification of RNA cis-regulatory sequences, IRAS, IMAGEtags, MERFISH, plant RNA labeling using MS2 and visualization of 5S dynamics in live cells using photostable corn probe

Tropomyosin

Tropomyosin PDF Author: Peter Gunning
Publisher: Springer Science & Business Media
ISBN: 0387857664
Category : Medical
Languages : en
Pages : 323

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Book Description
A recent review of one of my grant applications commented on the ‘rediscovery of tropomyosin’. I was tempted to write back in my rebuttal to the reviewer that I didn’t realise it had been lost. Uncharacteristic maturity prevailed and I resisted the temptation, but I was struck by the underlying observation that research on the str- ture and function of tropomyosin has been somewhat invisible, particularly in terms of the cytoskeleton isoforms. So, how can it be that one of the two major components of the actin filament has been so thoroughly overlooked? I suspect that the answer is disappointingly pedestrian. Whereas the biochemistry of the 1980s revealed the potential of tropomyosin isoforms to diversify the function of actin filaments, the subsequent disenchantment with isoform biology in general in the 1990s inhibited growth of this field. With the development of more sophisticated experimental - proaches we are now seeing a growing realisation of the importance of tropomyosin in regulating actin filaments beyond its pivotal role in muscle contraction. The opportunity to edit this book came at a time when we had written several reviews on different aspects of tropomyosin function and I had just finished the background reading for a comprehensive review of tropomyosin biology. I realised that the field was simply beyond the capacity of any one person to do the field j- tice.

Eukaryotic MRNA Processing

Eukaryotic MRNA Processing PDF Author: Adrian Krainer
Publisher: IRL Press
ISBN:
Category : Language Arts & Disciplines
Languages : en
Pages : 408

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Book Description
This volume focuses on the major aspects of post-transcriptional mRNA processing in the nucleus of eukaryotic cells. Each of the described mRNA reactions is required for proper gene expression and can also serve as a control point for regulating the expression of many genes, for example duringembryonic development or in different cell types. The different chapters review the assembly of newly synthesized nuclear mRNA transcripts into hnRNP particles and catalytically active spliceosomes; the structure and mechanism of action of small nuclear ribonucleoprotein particles and proteinfactors that catalyse pre-mRNA splicing in mammalian cells and in yeast; the regulation of gene expression and generation of protein isoform diversity by alternative splicing; the mechanisms of 3' end cleavage and polyadenylation; the architecture of the cell nucleus in relation to these processesand to the localization of the relevant substrates and factors; the diverse mechanisms of RNA processing by ribozymes and their potential relevance for nuclear mRNA processing; the mechanism of spliced-leader addition by trans-splicing in nematodes and trypanosomes; and the process ofinsertion/deletion mRNA editing in kinetoplasmid protozoa. In each chapter, leading researchers have provided detailed, critical reviews of the history, experimental approaches, major advances, current ideas and models, as well as future directions, for each of these active areas of research.

Alternative Splicing in Mammalian Brain

Alternative Splicing in Mammalian Brain PDF Author: Yida Zhang
Publisher:
ISBN:
Category :
Languages : en
Pages : 109

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Book Description
Post-transcriptional regulation is a set of important biological functions taking place during the genetic information flow from DNA to RNA. Alternative splicing is one of the post-transcriptional regulation mechanisms, which creates enormous diversity at the RNA level. Compared with other tissues, alternative splicing is highly abundant in brain. Emerging evidence shows that alternative splicing plays an important role in many neurological disorders. In this dissertation, the regulation of alternative splicing in mammalian brain and its relationship with neurological disorders was investigated. Based on our study, we demonstrated the importance of alternative splicing in neurological disorders, which provides insights of disease prevention and treatment. The first part of the dissertation studies the genetic regulation of alternative splicing in human brain and its implications in neurological disorders. A major question in genetics is how variants of ubiquitously expressed genes produce tissue- and cell type-specific phenotypes. One mechanism is through affecting alternative splicing that may contribute to disease. We investigated splicing quantitative trait loci (sQTLs) in 1,209 samples from 13 human brain regions, using RNA-seq and genotype data from the GTEx project. Hundreds of sQTLs were identified in each brain region. Some sQTLs were shared across brain regions, whereas others displayed regional specificity. These 'regionally ubiquitous' and 'regionally specific' sQTLs showed distinct positional distributions of single nucleotide polymorphisms (SNPs) within and outside essential splice sites, respectively, suggesting their regulation by divergent molecular mechanisms. Integrating the binding motifs and expression patterns of RNA binding proteins with exon splicing profiles, we uncovered likely causal variants of brain region specific sQTLs. Overall, our study reveals widespread regional variation of sQTLs in human brain, and demonstrates that such variation can be used to fine map causal variants of sQTLs and their associated neurological diseases. The second part of the dissertation focuses on sexual dimorphism of mammalian brain. Women and men showed difference in terms of neurological disorders. Previous studies investigated this sex difference using neuroanatomy and behavioral approaches. However, little is known about the underlying molecular mechanism. As an important post-transcriptional regulatory mechanism, we studied sexual dimorphic alternative splicing in mammalian brain through the female specific expression of the long noncoding RNA (lncRNA) Xist. This study is still ongoing.

Post-Transcriptional Gene Regulation

Post-Transcriptional Gene Regulation PDF Author: Jane Wu
Publisher: John Wiley & Sons
ISBN: 3527665412
Category : Science
Languages : en
Pages : 400

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Book Description
Reflecting the rapid progress in the field, the book presents the current understanding of molecular mechanisms of post-transcriptional gene regulation thereby focusing on RNA processing mechanisms in eucaryotic cells. With chapters on mechanisms as RNA splicing, RNA interference, MicroRNAs, RNA editing and others, the book also discusses the critical role of RNA processing for 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, clinics as well as pharmaceutical industry.