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Functional And Mechanistic Studies Of Adenosine Deaminases Acting On Rna
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Book Synopsis Functional and Mechanistic Studies of Adenosine Deaminases Acting on RNA by : Rena Aviva Mizrahi
Download or read book Functional and Mechanistic Studies of Adenosine Deaminases Acting on RNA written by Rena Aviva Mizrahi and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: ADARs (adenosine deaminases acting on RNA) are enzymes that catalyze the post-transcriptional deamination of adenosine to inosine in double-stranded RNA, a type of RNA editing. Inosine is recognized by the translation machinery as guanosine, so RNA editing can result in incorporation of different amino acids than those encoded in the genome. While some structural information is available for one enzyme in this family, ADAR2, there is a distinct lack of structural information regarding ADAR1. In addition, many questions exist regarding the biological function of these enzymes. In recent years new substrates for these enzymes have been identified, but their role is unknown. This dissertation describes experiments in which we work towards better understanding the mechanism and specificity of these enzymes, in the hopes of developing new tools to study A-to-I RNA editing. In the past our lab has extensively studied ADAR2, one member of this enzyme family. We have incorporated nucleoside analogues at the editing site to probe the active site, both before any structural information was available and afterwards to complement it. None of this was possible for ADAR1 until our recent characterization of a new ADAR1 substrate RNA, described in Chapter 2. Discovery and characterization of this editing site allowed us to develop an assay to probe the ADAR1 active site using nucleoside analogues. Chapter 3 details the development and use of this assay to uncover similarities and differences in how ADAR1 and ADAR2 recognize their substrate. These differences may pave the way for development of ADAR-specific inhibitors, and further use of this assay may allow us to uncover additional intriguing differences within this family of enzymes. With the abundance of new editing sites coming to light due to recent deep sequencing studies, more tools are needed to elucidate the biological consequences of these editing events. We developed substrate-specific inhibitors of editing by targeting RNA structure and sequence, described in Chapter 4. Importantly, we found that antisense oligonucleotides can bind to ADAR substrate RNAs, disrupt the native secondary structure and inhibit editing. We tested three different analogues and found that locked nucleic acid/2'-O-methyl mixmer oligonucleotides work most efficiently to inhibit editing. This will be an important new tool for the field, as labs can now use antisense oligonucleotides to inhibit editing of their RNA of choice. Finally, we developed several new assays for ADAR2 editing, for the most part based on the serotonin 2C receptor (5HT(2C)R) pre-mRNA. This work is described in Chapter 5. Similar assays have been used in the past with the GluR-B R/G site RNA, but adapting them to use the 5HT(2C)R RNA means that new sequence and secondary structure questions can now be addressed. In addition, we have used these assays to investigate how the part of ADAR2 linking the second double-stranded RNA binding domain and the catalytic domain may influence specificity and activity.
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 Mechanistic and Specificity Studies of the Isolated ADAR Deaminase Domains by : Jocelyn Virginia Havel
Download or read book Mechanistic and Specificity Studies of the Isolated ADAR Deaminase Domains written by Jocelyn Virginia Havel and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: ADARs (adenosine deaminases acting on RNA) are a family of RNA editing enzymes that catalyze the conversion of adenosine to inosine in double stranded RNA. Inosine is recognized as guanosine during translation, and thus A to I editing can lead to amino acids substitutions contributing to protein diversity. While there is some structural and mechanistic information available for one enzymes in this family, ADAR2, there is a distinct lack of information regarding ADAR1. This dissertation describes experiments that work towards better understanding the mechanism and specificity of these two enzymes. In the past, our lab has been able to independently study the deaminase domain of ADAR2 in the absence of the double-stranded RNA binding domains (dsRBDs) through discovery of the bromodomain factor 2 RNA substrate. This type of analysis is now possible for ADAR1 as we have recently identified BDF2 as a substrate for the ADAR1 isolated deaminase domain, described in Chapter 2. Characterization of this editing site has allowed us to develop an ADAR1 screening assay for identifying functional mutants. Chapter 3 details the use of the BDF2 substrate for nucleoside analog incorporation to make comparisons between nucleoside recognition by ADAR1 and ADAR2. It is still not clear why particular adenosines are selected for editing or how the deaminase domain interacts with dsRNA during deamination. The finding that the requirement for dsRBDs is substrate dependent has led to new editing substrates of the ADAR isolated deaminase domains. In Chapter 4, we have examined a human ADAR substrate that possess structural and sequence similarities to BDF2, hGLI1, and found that it too is edited by the deaminase domain of ADAR1. Finally, mutation of the G 3' of the edited A in hGLI1 revealed novel nearest neighbor preferences characteristic of the ADAR deaminase domains. This expands our understanding of how the deaminase domain influences specificity and activity.
Book Synopsis Hepatitis Delta Virus by : John L. Casey
Download or read book Hepatitis Delta Virus written by John L. Casey and published by Springer Science & Business Media. This book was released on 2006-09-02 with total page 231 pages. Available in PDF, EPUB and Kindle. Book excerpt: Hepatitis delta virus (HDV), which causes severe acute and chronic liver disease, was discovered nearly 30 years ago following the detection of a novel antigen-antibody system in hepatitis B virus carriers. HDV has continued to surprise and fascinate medical science ever since. This volume reviews recent developments in HDV research, from molecular virology to genetics to experimental investigation of new therapeutic and vaccine candidates.
Download or read book Biotransformations written by K. Faber and published by Springer Science & Business Media. This book was released on 2003-06-30 with total page 235 pages. Available in PDF, EPUB and Kindle. Book excerpt: Whereas the hydrolases such as proteases, esterases and lipases are sufficiently well researched to be applied in every standard laboratory, other types of enzymes are still waiting to be discovered with respect to their applicability in organic-chemistry transformations on a preparative scale. This latter point is stressed here, with the focus on the newcomer-enzymes'which show great synthetic potential.
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.
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 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.
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 Biomarkers in Inborn Errors of Metabolism by : Uttam Garg
Download or read book Biomarkers in Inborn Errors of Metabolism written by Uttam Garg and published by Elsevier. This book was released on 2017-06-07 with total page 477 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biomarkers of Inborn Errors in Metabolism: Clinical Aspects and Laboratory Determination is structured around the new reality that laboratory testing and biomarkers are an integral part in the diagnosis and treatment of inherited metabolic diseases. The book covers currently used biomarkers as well as markers that are in development. Because biomarkers used in the initial diagnosis of disease may be different than the follow-up markers, the book also covers biomarkers used in both the prognosis and treatment of inherited metabolic disorders. With the introduction of expanded new-born screening for inborn metabolic diseases, an increasing numbers of laboratories are involved in follow-up confirmatory testing. The book provides guidance on laboratory test selection and interpreting results in patients with suspected inherited metabolic diseases. The book provides comprehensive guidance on patient diagnosis and follow-up through its illustrative material on metabolic pathways, genetics and pathogenesis, treatment and prognosis of inherited metabolic diseases, along with essential information on clinical presentation. Each chapter is organized with a uniform, easy-to-follow format: a brief description of the disorder and pathway; a description of treatment; biomarkers for diagnosis; biomarkers followed for treatment efficacy; biomarkers followed for disease progression; confounding conditions that can either: affect biomarker expression or mimic IEMs; other biomarkers: less established, future. Provides comprehensive information on the tests/biomarkers selection in newborn screening and follow-up of newborn screens Categorizes biomarkers into diagnostic markers, disease follow-up markers, and prognostic biomarkers Covers confounding factors that can alter biomarkers in the absence of inborn errors of metabolism Offers guidance on how to distinguish acquired causes from inborn errors of metabolism
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 Genome Plasticity in Health and Disease by :
Download or read book Genome Plasticity in Health and Disease written by and published by Academic Press. This book was released on 2020-04-08 with total page 290 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genome Plasticity in Health and Disease provides a fully up-to-date overview on genome plasticity and its role in human physiology and disease. Following an introduction to the field, a diverse range of chapters cover genomic and epigenomic analysis and the use of model organisms and genomic databases in studies. Specific molecular and biochemical mechanisms of genome plasticity are examined, including somatic variants, De Novo variants, founder variations, isolated populations dynamics, copy-number variations, mobile elements, DNA methylation, histone modifications, transcription factors, non-coding RNAs, telomere dynamics and RNA editing. Later chapters explore disease relevance for cancer, as well as cardiovascular, neuropsychiatric, inflammatory, and endocrine disease, and associated pathways for drug discovery. Examines the role of genome plasticity across a range of disease types, from cardiovascular disease, to cancer and neuropsychiatric disorders Adopts an interdisciplinary approach, with expert contributions across the spectrum of basic science and disease relevance to drug discovery
Book Synopsis Molecular Biology of The Cell by : Bruce Alberts
Download or read book Molecular Biology of The Cell written by Bruce Alberts and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 Pediatric Allergy: Principles and Practice E-Book by : Donald Y. M. Leung
Download or read book Pediatric Allergy: Principles and Practice E-Book written by Donald Y. M. Leung and published by Elsevier Health Sciences. This book was released on 2010-10-13 with total page 705 pages. Available in PDF, EPUB and Kindle. Book excerpt: Pediatric Allergy supplies the comprehensive guidance you need to diagnose, manage, and treat virtually any type of allergy seen in children. Drs. Leung, Sampson, Geha, and Szefler present the new full-color second edition, with coverage of the diagnosis and management of anaphylaxis, the immune mechanisms underlying allergic disease, the latest diagnostic tests, and more. Treat the full range of pediatric allergic and immunologic diseases through clinically focused coverage relevant to both allergists and pediatricians. Understand the care and treatment of pediatric patients thanks to clinical pearls discussing the best approaches. Easily refer to appendices that list common food allergies and autoantibodies in autoimmune diseases. Apply the newest diagnostic tests available—for asthma, upper respiratory allergy, and more—and know their benefits and contraindications. Treat the allergy at its source rather than the resulting reactions through an understanding of the immune mechanisms underlying allergic diseases. Get coverage of new research that affects methods of patient treatment and discusses potential reasons for increased allergies in some individuals. Better manage potential anaphylaxis cases through analysis of contributing facts and progression of allergic disease. Effectively control asthma and monitor its progression using the new step-by-step approach. Eliminate difficulty in prescribing antibiotics thanks to coverage of drug allergies and cross-reactivity.
Download or read book Fungal RNA Biology written by Ane Sesma and published by Springer Science & Business Media. This book was released on 2014-04-15 with total page 396 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents an overview of the RNA networks controlling gene expression in fungi highlighting the remaining questions and future challenges in this area. It covers several aspects of the RNA-mediated mechanisms that regulate gene expression in model yeasts and filamentous fungi, organisms of great importance for industry, medicine and agriculture. It is estimated that there are more than one million fungal species on the Earth. Despite their diversity (saprophytic, parasitic and mutualistic), fungi share common features distinctive from plants and animals and have been grouped taxonomically as an independent eukaryotic kingdom. In this book, 15 chapters written by experts in their fields cover the RNA-dependent processes that take place in a fungal cell ranging from formation of coding and non-coding RNAs to mRNA translation, ribosomal RNA biogenesis, gene silencing, RNA editing and epigenetic regulation.
Book Synopsis Curing Genetic Diseases through Genome Reprogramming by :
Download or read book Curing Genetic Diseases through Genome Reprogramming written by and published by Academic Press. This book was released on 2021-06-24 with total page 560 pages. Available in PDF, EPUB and Kindle. Book excerpt: Curing Genetic Diseases through Genome Reprogramming, Volume 182 captures an historic moment in the field of gene therapy—the dawn of a new age in which the dream of curing genetic diseases has become realizable. The volume presents the most clinically advanced gene therapy and genome editing approaches for the treatment of genetic diseases in specific organs, including difficult therapeutic targets, futuristic ideas of genetic interventions, and large scale human genome repair. An initial chapter addresses the complex ethical aspects involved in the very idea of modifying the human genome. Provides a comprehensive view of gene therapy and genome editing technologies, including epigenetic editing Describes the state-of-the-art and future directions for the treatment of genetic diseases, also considering economical aspects Presents chapters that each give a thorough review of a specific disease, target organ or visionary approach, including ethical considerations
