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Structural Basis For Rna Editing And Site Selectivity By Adar2
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Book Synopsis Structural Basis for RNA Editing and Site Selectivity by ADAR2 by : Justin Mclntyre Thomas
Download or read book Structural Basis for RNA Editing and Site Selectivity by ADAR2 written by Justin Mclntyre Thomas and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Adenosine deaminases acting on RNA (ADARs) are RNA editing enzymes that convert adenosine to inosine in duplex RNA. Because inosine behaves like guanosine in Watson-Crick base pairing, A-to-I editing may have wide ranging consequences in RNA function. The X-ray crystal structure of the deaminase domain of one member of the ADAR family (ADAR2) was solved over a decade ago, however this structure lacked RNA and provided limited information on how ADARs select, bind and edit adenosines within duplex RNA. This dissertation describes solving of X-ray co-crystal structures of ADAR2’s deaminase domain bound to synthetic duplex RNA and subsequent experiments to define the structural basis of the enzymes sequence preferences. Chapter 2 describes the solved crystal structures of ADAR2 deaminase domain-RNA complexes. The deaminase domain’s RNA binding interface is analyzed and new RNA binding residues are identified. In Chapter 3 the importance of newly identified RNA binding residues is examined through in-vitro biochemical assays. The structural basis for ADAR2’s nearest neighbor sequence preferences are also defined by probing contacts made to the RNA using chemically modified RNA substrates. This information may aid the development of systems to direct A-to-I editing of specific adenosines using ADARs. In Chapter 4, RNA binding experiments using ADAR2 constructs bearing double stranded RNA binding domains (dsRBDs) are carried out with the goal of better understanding how the dsRBDs affect the specificity and behavior of the full length ADAR2. Mobility shift assays, RNA cleavage footprinting assays and electron microscopy all provide evidence that ADAR2 undergoes a specific RNA dependent dimerization. Finally, efforts to obtain high resolution structural data for ADAR2 constructs bearing dsRBDs through X-ray crystallography and Cryo-electron microscopy are discussed
Book Synopsis Structures of Human ADAR2 Bound to DsRNA Reveal Base-flipping Mechanism and Basis for Site Selectivity by :
Download or read book Structures of Human ADAR2 Bound to DsRNA Reveal Base-flipping Mechanism and Basis for Site Selectivity written by and published by . This book was released on 2016 with total page 8 pages. Available in PDF, EPUB and Kindle. Book excerpt: Adenosine deaminases acting on RNA (ADARs) are editing enzymes that convert adenosine to inosine in duplex RNA, a modification reaction with wide-ranging consequences in RNA function. Understanding of the ADAR reaction mechanism, the origin of editing-site selectivity, and the effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. In this paper, we describe four crystal structures of the human ADAR2 deaminase domain bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis of the ADAR deaminase domain's dsRNA specificity, its base-flipping mechanism, and its nearest-neighbor preferences. In addition, we identified an ADAR2-specific RNA-binding loop near the enzyme active site, thus rationalizing differences in selectivity observed between different ADARs. In conclusion, our results provide a structural framework for understanding the effects of ADAR mutations associated with human disease.
Book Synopsis Fine-Tuning of RNA Functions by Modification and Editing by : Henri Grosjean
Download or read book Fine-Tuning of RNA Functions by Modification and Editing written by Henri Grosjean and published by Springer. This book was released on 2005-05-11 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Naturally occurring RNA always contains numerous biochemically altered nucleotides. They are formed by enzymatic modification of the primary transcripts during the complex RNA maturation process designated RNA modification. A large number of enzymes catalyzing the formation of these modified nucleosides or converting one canonical base into another at the posttranscriptional level have been studied for many years, but only recently have systematic and comparative studies begun. The functions of individual enzymes and/or the modified/edited nucleosides in RNA, however, have remained largely ignored. This book provides advance information on RNA modification, including the associated editing machinery, while offering the reader some perspective on the significance of such modifications in fine-tuning the structure and functions of mature RNA molecules and hence the ability to influence the efficiency and accuracy of genetic expression. Outstanding scientists who are actively working on RNA modification/editing processes have provided up-to-date information on these intriguing cellular processes that have been generated over the course of millions of years in all living organisms. Each review has been written and illustrated for a large audience of readers, not only specialists in the field, but also for advanced students or researchers who want to learn more about recent progress in RNA modification and editing.
Book Synopsis Adenosine Deaminases Acting on RNA (ADARs) and A-to-I Editing by : Charles E. Samuel
Download or read book Adenosine Deaminases Acting on RNA (ADARs) and A-to-I Editing written by Charles E. Samuel and published by Springer Science & Business Media. This book was released on 2011-11-06 with total page 244 pages. Available in PDF, EPUB and Kindle. Book excerpt: “The objective of this CTMI volume is to provide readers with a foundation for understanding what ADARs are and how they act to affect gene expression and function. It is becoming increasingly apparent that ADARs may possess roles not only as enzymes that deaminate adenosine to produce inosine in RNA substrates with double-stranded character, but also as proteins independent of their catalytic property. Because A-to-I editing may affect base-pairing and RNA structure, processes including translation, splicing, RNA replication, and miR and siRNA silencing may be affected. Future studies of ADARs no doubt will provide us with additional surprises and new insights into the modulation of biological processes by the ADAR family of proteins.”
Book Synopsis RNA-protein Interactions by : Kiyoshi Nagai
Download or read book RNA-protein Interactions written by Kiyoshi Nagai and published by Oxford University Press, USA. This book was released on 1994 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt: The study of RNA-protein interactions is crucial to understanding the mechanisms and control of gene expression and protein synthesis. The realization that RNAs are often far more biologically active than was previously appreciated has stimulated a great deal of new research in this field. Uniquely, in this book, the world's leading researchers have collaborated to produce a comprehensive and current review of RNA-protein interactions for all scientists working in this area. Timely, comprehensive, and authoritative, this new Frontiers title will be invaluable for all researchers in molecular biology, biochemistry and structural biology.
Book Synopsis Gene Therapy in Lung Disease by : Steven M. Albeda
Download or read book Gene Therapy in Lung Disease written by Steven M. Albeda and published by CRC Press. This book was released on 2002-09-20 with total page 582 pages. Available in PDF, EPUB and Kindle. Book excerpt: Presents up-to-date summaries of recently completed and ongoing clinical trials. With writings from more than 35 internationally renowned experts, Gene Therapy in Lung Disease unlocks the biological mysteries of infection immunity cytokine behavior fibrosis and illustrates the use of gene the
Book Synopsis RNA Metabolism in Neurodegenerative Diseases by : Rita Sattler
Download or read book RNA Metabolism in Neurodegenerative Diseases written by Rita Sattler and published by Springer. This book was released on 2018-06-18 with total page 310 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book RNA Editing written by and published by Elsevier. This book was released on 2007-08-01 with total page 591 pages. Available in PDF, EPUB and Kindle. Book excerpt: RNA processing plays a critical role in realizing the full potential of a given genome. One means of achieving protein diversity is through RNA editing. A diverse array of editing events has been characterized, affecting gene expression in organisms from viruses and single cell parasites to humans and plants. The variety of editing mechanisms has required the development of many different experimental approaches, many of which are likely to be broadly applicable, particularly given the interplay between editing and other cellular processes, including transcription, splicing, and RNA silencing. RNA Editing not only covers most of the principal methods employed in the field, but also offers innovative solutions to the significant challenges posed by these experimental systems. Presents newly developed methods Covers topics ranging from biochemistry to bioinformatics Includes innovative solutions to potential problems
Download or read book RNA Editing written by Ernesto Picardi and published by Humana. This book was released on 2021-08-13 with total page 352 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume provides an overview about main RNA editing mechanisms, focusing on their functions in physiological as well as pathological conditions. Chapters guide readers through state- of-the art methodologies to investigate RNA editing through wet and dry approaches. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, RNA Editing: Methods and Protocols aims to ensure successful results in the further study of this vital field.
Download or read book RNA Editing written by H. Ulrich Göringer and published by Springer Science & Business Media. This book was released on 2008-01-12 with total page 239 pages. Available in PDF, EPUB and Kindle. Book excerpt: Goringer’s brilliant new work dedicates a chapter to each of the main types of RNA editing – the very first volume to do so. All of the sections here have been written by experts in the various research areas and a specific focus is put on the correlation between RNA structure and function, as well as on the complex cellular machineries that catalyze the different editing reactions. This leads to a "state of the art" compendium of our current knowledge on RNA editing.
Book Synopsis Epitranscriptomics by : Stefan Jurga
Download or read book Epitranscriptomics written by Stefan Jurga and published by Springer Nature. This book was released on 2021-07-28 with total page 632 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book reviews a novel and exciting field of cellular and molecular biology called epitranscriptomics, which focuses on changes in an organism’s cells resulting from the posttranscriptional modification of cellular RNA. RNA-binding proteins (RBPs) play a crucial role in these posttranscriptional modifications and also support several cellular processes necessary for maintaining RNA homeostasis. Exploring the mechanisms underlying RNA modifications and RBP function is an emerging area of biomedical research, taking the study of gene regulation a step beyond epigenetics. This book reveals that the RNA molecule is not just an information-carrying molecule with some secondary structures. Accordingly, how RNA is modified, regulated, packaged, and controlled is an important aspect. Leading experts address questions such as where the over 170 distinct posttranscriptional RNA modifications are located on the genome, what percentage of mRNAs and noncoding RNAs these modifications include, and how an RNA modification impacts a person’s biology. In closing, the book reviews the role of RNA modifications and RBPs in a variety of diseases and their pathogenesis. Addressing some of the most exciting challenges in epitranscriptomics, this book provides a valuable and engaging resource for researchers in academia and industry studying the phenomena of RNA modification.
Book Synopsis Evolutionary Biology—A Transdisciplinary Approach by : Pierre Pontarotti
Download or read book Evolutionary Biology—A Transdisciplinary Approach written by Pierre Pontarotti and published by Springer Nature. This book was released on 2020-10-29 with total page 389 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book includes 16 selected contributions presented at the 23rd Evolutionary Biology Meeting, which took place in Marseille in September 2019. The annual Evolutionary Biology Meetings in Marseille serve to gather leading evolutionary biologists and other scientists using evolutionary biology concepts, e.g. for medical research. The aim of these meetings is to promote the exchange of ideas to encourage interdisciplinary collaborations. Offering an up-to-date overview of recent findings in the field of evolutionary biology, this book is an invaluable source of information for scientists, teachers and advanced students.
Book Synopsis DNA and RNA Modification Enzymes by : Henri Grosjean
Download or read book DNA and RNA Modification Enzymes written by Henri Grosjean and published by CRC Press. This book was released on 2009-06-11 with total page 682 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume is a timely and comprehensive description of the many facets of DNA and RNA modification-editing processes and to some extent repair mechanisms. Each chapter offers fundamental principles as well as up to date information on recent advances in the field (up to end 2008). They ended by a short ‘conclusion and future prospect’ section and an exhaustive list of 35 to up to 257 references (in average 87). Contributors are geneticists, structural enzymologists and molecular biologists working at the forefront of this exciting, fast-moving and diverse field of researches. This book will be a major interest to PhD students and University teachers alike. It will also serve as an invaluable reference tool for new researchers in the field, as well as for specialists of RNA modification enzymes generally not well informed about what is going on in similar processes acting on DNA and vice-versa for specialists of the DNA modification-editing and repair processes usually not much acquainted with what is going on in the RNA maturation field. The book is subdivided into 41 chapters (740 pages). The common links between them are mainly the enzymatic aspects of the different modification-editing and repair machineries: structural, mechanistic, functional and evolutionary aspects. It starts with two general and historical overview of the discovery of modified nucleosides in DNA and RNA and corresponding modification-editing enzymes. Then follows eleven chapters on DNA modification and editing (mechanistic and functional aspects). Two additional chapters cover problems related to DNA/RNA repair and base editing by C-to-U deaminases, followed by three chapters on RNA editing by C-to-U and A-to-I type of deamination. Discussions about interplay between DNA and RNA modifications and the emergence of DNA are covered in two independent chapters, followed by twenty chapters on different but complementary aspects of RNA modification enzymes and their cellular implications. The last chapter concerns the description of the present state-of-the art for incorporating modified nucleosides by in vitro chemical synthesis. At the end of the book, six appendicies give useful details on modified nucleosides, modification-editing enzymes and nucleosides analogs. This information is usually difficult to obtain from current scientific literature.
Book Synopsis CRISPR-Cas Systems by : Rodolphe Barrangou
Download or read book CRISPR-Cas Systems written by Rodolphe Barrangou and published by Springer Science & Business Media. This book was released on 2012-12-13 with total page 300 pages. Available in PDF, EPUB and Kindle. Book excerpt: CRISPR/Cas is a recently described defense system that protects bacteria and archaea against invasion by mobile genetic elements such as viruses and plasmids. A wide spectrum of distinct CRISPR/Cas systems has been identified in at least half of the available prokaryotic genomes. On-going structural and functional analyses have resulted in a far greater insight into the functions and possible applications of these systems, although many secrets remain to be discovered. In this book, experts summarize the state of the art in this exciting field.
Book Synopsis RNA Damage and Repair by : Ioly Kotta-Loizou
Download or read book RNA Damage and Repair written by Ioly Kotta-Loizou and published by Springer Nature. This book was released on 2021-07-04 with total page 180 pages. Available in PDF, EPUB and Kindle. Book excerpt: Ribonucleic acid (RNA) is a macromolecule that plays a central role in cell physiology: RNA molecules act as intermediates between the deoxyribonucleic acid (DNA), where genetic information is stored, and proteins, which perform the necessary functions within the cell. Traditionally, the structural and functional properties of RNA are closely linked to gene expression. However, RNA-based enzymes, called ribozymes, are also involved in catalysis and small RNAs regulate key cellular processes, such as cell growth, division, differentiation, aging and death. RNA is a sensitive macromolecule that can be easily damaged by environmental conditions (ultraviolet radiation, oxidative stress) and biological factors (ribonucleases, ribotoxins, CRISPR-Cas systems). Therefore, cells have developed mechanisms to protect and/or repair RNA molecules. This book presents an overview of the biology of RNA damage, protection and repair in prokaryotes and eukaryotes. Individual chapters cover the expression regulation, enzymology and physiological role of such systems, and link them to important human diseases such as cancer and degenerative diseases.
Book Synopsis Modification and Editing of RNA by : Henri Grosjean
Download or read book Modification and Editing of RNA written by Henri Grosjean and published by . This book was released on 1998 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This Comprehensive, current text explores the manifold ways in which living cells respond to genomic injury and alterations, including both spontaneous and environmentally induced DNA damage. With more than 4,000 complete references to primary research literature and over 380 color figures throughout, this book is an important text for all courses in DNA repair and mutagenesis. It will also serve as a major reference for all molecular biologists working in cancer biology, recombination, transcription and gene regulation, DNA replication, environmental studies, and biological evolution.
Book Synopsis Non-Protein Coding RNAs by : Nils Walter
Download or read book Non-Protein Coding RNAs written by Nils Walter and published by Springer Science & Business Media. This book was released on 2008-11-18 with total page 400 pages. Available in PDF, EPUB and Kindle. Book excerpt: The 2006 Nobel Prize in Physiology or Medicine was awarded to the discoverers of RNA interference, Andrew Fire and Craig Mello. This prize, which follows “RNA” Nobels for splicing and RNA catalysis, highlights just one class of recently discovered non-protein coding RNAs. Remarkably, non-coding RNAs are thought to outnumber protein coding genes in mammals by perhaps as much as four-fold. In fact, it appears that the complexity of an organism correlates with the fraction of its genome devoted to non-protein coding RNAs. Essential biological processes as diverse as cell differentiation, suppression of infecting viruses and parasitic tra- posons, higher-level organization of eukaryotic chromosomes, and gene expression are found to be largely directed by non-protein coding RNAs. Currently, bioinformatic, high-throughput sequencing, and biochemical approaches are identifying an increasing number of these RNAs. Unfortunately, our ability to characterize the molecular details of these RNAs is significantly lacking. The biophysical study of these RNAs is an emergent field that is unraveling the molecular underpinnings of how RNA fulfills its multitude of roles in sustaining cellular life. The resulting understanding of the physical and chemical processes at the molecular level is critical to our ability to harness RNA for use in biotechnology and human therapy, a prospect that has recently spawned a multi-billion dollar industry.
