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Understanding Unique Features Of Human Adenosine Deaminases Acting On Rna
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Book Synopsis Understanding Unique Features of Human Adenosine Deaminases Acting on RNA by : SeHee Park
Download or read book Understanding Unique Features of Human Adenosine Deaminases Acting on RNA written by SeHee Park and published by . This book was released on 2020 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Adenosine Deaminases that act on RNA (ADARs) are a family of enzymes that convert adenosine to inosine in dsRNA which is a common form of RNA editing. Because inosine is recognized as guanosine by cellular machinery, there are numerous consequences resulting from ADAR mediated A-to-I editing including protein recoding event. Therefore, proper ADAR activity is necessary for several cellular processes. In fact, it has been shown that aberrant activities of ADARs can lead to various human diseases such as cancer and neurological disorders. It is especially important to understand ADAR1's biological function and activity because ADAR1 plays an essential role in innate immunity and it is a potential therapeutic target for a subset of cancers based on several recent studies. Although our understanding of ADARs has been significantly improved over a few decades, there are still important questions that need to be answered, especially regarding ADAR1 activity and its interaction with RNA substrates to better understand its biological roles in humans. This dissertation describes the exploration of unique features of human ADARs that could affect their catalytic activity as well as substrate recognition through several biochemical experiments and the attempts for structural characterization of ADARs. In chapter 1, an overview of RNA editing and its consequences are described with respect to A-to-I editing mediated by ADARs, highlighting its catalytic activity, substrate selectivity, and biological consequences that are linked to various human diseases. More details on the biological role of ADAR1 in humans are included to further emphasize the importance of understanding ADAR1 biology. Chapter 2 describes the high-throughput functional screening of the 5' binding loop of ADAR1. The 5' binding loop of ADARs plays an important role in RNA recognition. Yet, its sequence is substantially different among ADARs. Therefore, this work helps us better understand the selectivity difference between ADAR1 and ADAR2. Chapter 3 is focused on the exploration of covalent crosslinking, which takes advantage of a disulfide bond formation between the Cys mutant of ADARs and thiol modified dsRNA to stabilize various ADAR-dsRNA complexes for biophysical characterization. Various novel thiol modified nucleoside analogs are utilized to optimize covalent crosslinking of ADARs and the results suggest this strategy has the potential to advance our knowledge of ADARs through structural studies. Chapter 4 describes the discovery of a second metal binding site that is unique to ADAR1 and important for its catalytic activity along with the computational modeling of the ADAR1 deaminase domain structure using this novel feature of ADAR1. These collaborative works provide more insight into the unique properties of ADAR1. In Chapter 5, the optimization of ADAR1 catalytic domain purification is described in detail that leads to several crystallization trials for biophysical characterization of the ADAR1 deaminase domain through X-ray crystallography. Moreover, results from a binding study with a duplex RNA containing an adenosine analog, 8-azanebularine, further provide an additional approach to stabilize the ADAR1-dsRNA complex for X-ray crystallography. Lastly, inhibition of ADARs activity was investigated using various small molecules, which is discussed in Chapter 6.
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 Substrate Recognition and Novel Substrate Discovery for Human Adenosine Deaminase that Acts on Double-stranded RNA by : Yuxuan Zheng
Download or read book Substrate Recognition and Novel Substrate Discovery for Human Adenosine Deaminase that Acts on Double-stranded RNA written by Yuxuan Zheng 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 a family of enzymes that is responsible for the adenosine to inosine conversions within duplex RNA. Inosine is a commonly occurring modified nucleoside in human RNAs and it preferentially base pairs with cytidine. A proper level of inosine modification present in RNA is important for cellular functions and dysregulated adenosine to inosine conversions are related to various diseases. My studies mostly focused on human ADAR enzymes. Much of our current understanding of ADAR proteins originated from knowledge of their substrates. Therefore, developing novel methods to identify ADAR substrates will certainly advance the field. In Chapter 2 and Chapter 3, I describe two novel methods that could be used to identify new substrates for ADARs. Both of these methods are designed using nucleoside analogs. The nucleoside analog discussed in Chapter 2, 8-aza-7-deaza-7 ethynyl adenosine, could be used for RNA secondary structure probing. The structurally flexible adenosines identified through this method have a high potential to be substrates for ADARs. The nucleoside analog discussed in Chapter 3, 8-azanebularine, was used to identify ADAR substrates based on their affinity for the enzymes. Understanding the substrate recognition of ADARs is also beneficial for novel substrate identification. In Chapter 4, I discuss several interactions between the RNA substrate and the ADAR protein. These interactions were first identified in a substrate bound ADAR2 catalytic domain crystal structure. These studies highlighted some important residues for substrate binding and nearest neighbor recognition. With the help of the substrate bound ADAR structure, a new class of substrate was discovered that is discussed in Chapter 5. I showed not only that ADARs are capable of deaminating DNA/RNA hybrids, but also that ADAR systems can be used for RNA directed DNA deamination. Although future studies are needed to confirm that such reactions can occur in cells and to develop these systems to target DNA deamination in double-stranded DNA, the work described in Chapter 5 certainly expands the potential biological functions and biotechnology applications for ADARs. Lastly, the chemically modified nucleoside containing RNAs were also used in studies for other nucleic acid modifying enzymes as well, which is discussed in Chapter 6. These modifications were successfully used to illustrate catalytic mechanisms, enhance efficacy and reduce undesired interactions for several enzymes.
Book Synopsis RNA Recognition by Adenosine Deaminases Acting on RNA by : Yuru Wang
Download or read book RNA Recognition by Adenosine Deaminases Acting on RNA written by Yuru Wang 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 (ADAR) catalyze adenosine to inosine changes in double stranded RNAs, a type of post-transcriptional modification that can change the codon meaning and contribute to protein diversity in higher organisms. This modification is also known to regulate the fate of the RNA, including its expression, turnover, involvement in RNA interference and so forth. Three types of ADARs have been found in mammals, with ADAR1 and ADAR2 being catalytically active whereas ADAR3 being considered catalytically inactive. Malfunctions of ADARs have been correlated with various human diseases, including cancer. The Beal lab over the years has devoted extensive efforts in elucidating how ADARs recognize RNA substrates, and understanding the mechanism behind the RNA recognition difference between ADAR1 and ADAR2. These efforts not only advance our understanding of how these enzymes function, but also pave the way for future development of ADAR specific inhibitors of therapeutic significance. This thesis is a continuation of these efforts contributing to our understanding of how these fascinating enzymes function and providing new tools for future studies of them. Chapter 1 is an introduction of background knowledge about A-to-I RNA editing and ADAR. Chapter 2 introduced a new phenotypic reporter system that utilizes an RNA substrate efficiently processed by both ADAR1 and ADAR2 catalytic domains (ADAR-D) and a study utilizing this reporter to probe the RNA recognition by the base flipping residue in ADAR1. On the basis of this reporter system, in Chapter 3, a fluorescent reporter assay was developed to achieve high-throughput and quantitative evaluation of ADAR editing activity never achieved by other assays before, and a method called Sat-FACS-seq was introduced which provides information-rich landscape of sequence requirement across any region in ADARs. Applying this method to the 5’ binding loop of ADAR2, a novel insight into how this loop recognizes RNA was obtained. Chapter 4 detailed a study on the RNA secondary structural features that could distinguish ADAR1-D editing from ADAR2-D editing. Experimental evidence was shown, for the first time, to prove that the 5’ binding loops contribute to the site selectivity difference between ADAR1 and ADAR2, probably through differential recognition of RNA structure in the region 5’ from the editing site. Lastly, in Chapter 5, an effort to evolve the inactive ADAR3 into an active deaminase was described. Our success in turning ADAR3 into an active deaminase not only provides structural explanation of why wild-type ADAR3 is catalytically inactive, but also advances our knowledge of important residues required for proper ADAR function other than the ones traditionally appreciated. Moreover, the active ADAR3 mutant obtained was introduced with a minimal number of mutations (five), none of which was located in the RNA binding domains or on the primary RNA recognition surfaces. Thus, the mutant would be of great value for identifying the cellular binding targets of ADAR3 in vivo, which is important for understanding its biological function.
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.
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
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 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.
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 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
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 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 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 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
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 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 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.
