Nucleic Acids and Molecular Biology – serie

The literature on recoding is scattered, so this superb book ?lls a need by prov- ing up-to-date, comprehensive, authoritative reviews of the many kinds of recoding phenomena. Between 1961 and 1966 my colleagues and I deciphered the genetic code in Escherichia coli and showed that the genetic code is the same in E. coli, Xenopus laevis, and guinea pig tissues. These results showed that the code has been c- served during evolution and strongly suggested that the code appeared very early during biological evolution, that all forms of life on earth descended from a c- mon ancestor, and thus that all forms of life on this planet are related to one another. The problem of biological time was solved by encoding information in DNA and retrieving the information for each new generation, for it is easier to make a new organism than it is to repair an aging, malfunctioning one. Subsequently, small modi?cations of the standard genetic code were found in certain organisms and in mitochondria. Mitochondrial DNA only encodes about 10–13 proteins, so some modi?cations of the genetic code are tolerated that pr- ably would be lethal if applied to the thousands of kinds of proteins encoded by genomic DNA.

The literature on recoding is scattered, so this superb book ?lls a need by prov- ing up-to-date, comprehensive, authoritative reviews of the many kinds of recoding phenomena. Between 1961 and 1966 my colleagues and I deciphered the genetic code in Escherichia coli and showed that the genetic code is the same in E. coli, Xenopus laevis, and guinea pig tissues. These results showed that the code has been c- served during evolution and strongly suggested that the code appeared very early during biological evolution, that all forms of life on earth descended from a c- mon ancestor, and thus that all forms of life on this planet are related to one another. The problem of biological time was solved by encoding information in DNA and retrieving the information for each new generation, for it is easier to make a new organism than it is to repair an aging, malfunctioning one. Subsequently, small modi?cations of the standard genetic code were found in certain organisms and in mitochondria. Mitochondrial DNA only encodes about 10–13 proteins, so some modi?cations of the genetic code are tolerated that pr- ably would be lethal if applied to the thousands of kinds of proteins encoded by genomic DNA.

The origin of life is one of the biggest unsolved scientific questions. This book deals with the formation and first steps of the chemical evolution of nucleic acids, including the chemical roots behind the origin of their components from the simplest sources in a geochemical context. Chemical evolution encompasses the chemical processes and interactions conducive to self-assembly and supramolecular organization, leading to an increase of complexity and the emergence of life. The book starts with a personal account of the pioneering work of Stanley Miller and Jeffrey Bada on the Chemistry of Origins of Life and how the development of organic chemistry beginning in the 19th century led to the emergence of the field of prebiotic chemistry, situated at the frontier between organic, geo- and biochemistry. It then continues reviewing in tutorial manner current central topics regarding the organization of nucleic acids: the origin of nucleobases and nucleosides, their phosphorylation and polymerization and ultimately, their self-assembly and supramolecular organization at the inception of life.

Dysfunction of nuclear-cytoplasmic transport systems has been associated with many human diseases. Thus, understanding of how functional this transport system maintains, or through dysfunction fails to maintain remains the core question in cell biology.

This volume focuses on mitochondrial RNA metabolism, emphasizing recent discoveries and technological advances in this fast moving area that increase our understanding of mitochondrial gene function. Several RNA processes and machineries in protozoa, plants, flies and humans are discussed, including: transcription and RNA polymerase mechanism;

This volume focuses on recent advancements in our current understanding of nucleic acid photochemistry and its relationship to biologically relevant phenomena. Understanding the photophysical properties of nucleic acids is an area of longstanding and active research. Over the years, the field has greatly benefitted from steady advances in spectroscopic techniques and computational methods to study molecular excited states, which have facilitated detailed studies of the behavior of nucleic acids and their components after they absorb light. Experiments performed on ultrafast time scales (femtoseconds - picoseconds) have permitted the accurate determination of excited state lifetimes, while computational studies have provided detailed microscopic information about the mechanisms involved. As our understanding of the fundamental photophysics of nucleic acids has advanced, current studies now focus on systems of higher complexity, and introduce novel optical techniques to investigate the interactions between nucleic acids and proteins. Spectroscopic studies of nucleic acids, particularly nucleic acid constructs labeled with optical probes, can yield richly detailed information important to molecular biology, biochemistry and biophysics.This book is a must-read for anyone interested in the photophysical properties of nucleic acids and their role in biologically relevant phenomena.

This book provides an insightful journey into the realm of chloroplast biology. Chloroplasts are the organelles that perform photosynthesis and many of the metabolic processes in plant cells. They are a specialized form of plastids, whose differentiation is dependent on environmental and developmental signaling. Descended from a lineage of free-living, photosynthesizing prokaryotes, chloroplasts and other plastids contain remnants of their ancient genomes and chloroplast gene expression is essential for establishing functional organelles. Chloroplast gene expression has features of the prokaryotic gene expression but now involves large suites of nuclear proteins.Topics discussed are:the identification of these nuclear factorshow chloroplast RNA is processed to produce functional organellestranslation in chloroplasts and its regulationthe environmental factors that influence chloroplast developmentand how plants deal with defective chloroplasts.The book also highlights the evolving landscape of chloroplast engineering in biotechnology, recent breakthroughs and their implications for the future.A valuable resource for researchers, students, and enthusiasts alike, this book is a compelling testament to the fascinating world of chloroplasts and their burgeoning role in scientific innovation.

This book provides an insightful journey into the realm of chloroplast biology. Chloroplasts are the organelles that perform photosynthesis and many of the metabolic processes in plant cells. They are a specialized form of plastids, whose differentiation is dependent on environmental and developmental signaling. Descended from a lineage of free-living, photosynthesizing prokaryotes, chloroplasts and other plastids contain remnants of their ancient genomes and chloroplast gene expression is essential for establishing functional organelles. Chloroplast gene expression has features of the prokaryotic gene expression but now involves large suites of nuclear proteins.Topics discussed are:the identification of these nuclear factorshow chloroplast RNA is processed to produce functional organellestranslation in chloroplasts and its regulationthe environmental factors that influence chloroplast developmentand how plants deal with defective chloroplasts.The book also highlights the evolving landscape of chloroplast engineering in biotechnology, recent breakthroughs and their implications for the future.A valuable resource for researchers, students, and enthusiasts alike, this book is a compelling testament to the fascinating world of chloroplasts and their burgeoning role in scientific innovation.

With the advent of next-generation sequencing technologies, the genomic sequences for an ever-expanding number of organisms have been decoded, providing immense databases of protein amino acid sequences and DNA and RNA nucleotide sequences. These databases are allowing comparisons across thousands of species, enabling the identification of those that have undergone significant molecular evolution in specific proteins or RNA molecules.  In the 21st century, RNA biology has gained major attention with the discovery of functional non-coding RNAs and regulatory systems including CRISPR. These advances have clarified with high resolution the evolutionary transitions of RNA-related enzymes and RNA-binding proteins, which govern the flow of genetic information. This book provides an in-depth overview on the molecular evolution of RNA-related enzymes, RNA-binding proteins, and RNA regulatory systems. The focus is not only on newly-identified RNA regulatory factors or systems that have garnered attention since the beginning of the 21st century, but it also elucidates RNA-related molecules with fundamental and significant roles in cellular genetic regulation, or the regulatory systems themselves. Specifically, the volume revisits molecules involved in transcription (RNA polymerase), pre-mRNA processing and degradation (ribonucleases such as RNase E, RNase III, and self-cleaving ribozymes), and in translation (ribosomal proteins and translation factors), regardless of their novelty. This volume thus is intended to serve as an essential resource for furthering the systematic understanding of cellular genetic regulation from a molecular evolutionary standpoint.

This book spans diverse aspects of modified nucleic acids, from chemical synthesis and spectroscopy to in vivo applications, and highlights studies on chemical modifications of the backbone and nucleobases. Topics discussed include fluorescent pyrimidine and purine analogs, enzymatic approaches to the preparation of modified nucleic acids, emission and electron paramagnetic resonance (EPR) spectroscopy for studying nucleic acid structure and dynamics, non-covalent binding of low- and high-MW ligands to nucleic acids and the design of unnatural base pairs. This unique book addresses new developments and is designed for graduate level and professional research purposes.

This book focuses on the regulation of transcription and translation in Archaea and arising insights into the evolution of RNA processing pathways. From synthesis to degradation and the implications of gene expression, it presents the current state of knowledge on archaeal RNA biology in 13 chapters. Topics covered include the modification and maturation of RNAs, the function of small non-coding RNAs and the CRISPR-Cas defense system. While Archaea have long been considered exotic microbial extremophiles, they are now increasingly being recognized as important model microorganisms for the study of molecular mechanisms conserved across the three domains of life, and with regard to the relevance of similarities and differences to eukaryotes and bacteria. This unique book offers a valuable resource for all readers interested in the regulation of gene expression in Archaea and RNA metabolism in general.

Dysfunction of nuclear-cytoplasmic transport systems has been associated with many human diseases. Thus, understanding of how functional this transport system maintains, or through dysfunction fails to maintain remains the core question in cell biology. In eukaryotic cells, the nuclear envelope (NE) separates the genetic transcription in the nucleus from the translational machinery in the cytoplasm. Thousands of nuclear pore complexes (NPCs) embedded on the NE selectively mediate the bidirectional trafficking of macromolecules such as RNAs and proteins between these two cellular compartments. In this book, the authors integrate recent progress on the structure of NPC and the mechanism of nuclear-cytoplasmic transport system in vitro and in vivo.

This volume focuses on mitochondrial RNA metabolism, emphasizing recent discoveries and technological advances in this fast moving area that increase our understanding of mitochondrial gene function. Topics addressed include the interplay of mitochondria with the nucleus and cytosol, structure-function connections, and relevance to human disease. Mitochondria are the powerhouses of the cell, and a great deal is known about mitochondrial energy metabolism. Less well known is the plethora of amazing mechanisms that have evolved to control expression of mitochondrial genomes. Several RNA processes and machineries in protozoa, plants, flies and humans are discussed, including: transcription and RNA polymerase mechanism; tRNA processing of 5′ and 3′ ends; mRNA maturation by nucleotide insertion/deletion editing and by RNA splicing; mRNA stability; and RNA import. Specialized factors and ribonucleoproteins (RNPs) examined include pentatricopeptide repeat (PPR) proteins, RNase P, polymerases,helicases, nucleases, editing and repair enzymes. Remarkable features of these processes and factors are either not found outside mitochondria, differ substantially among eukaryotic lineages, or are unique in biology.

This book spans diverse aspects of modified nucleic acids, from chemical synthesis and spectroscopy to in vivo applications, and highlights studies on chemical modifications of the backbone and nucleobases. Topics discussed include fluorescent pyrimidine and purine analogs, enzymatic approaches to the preparation of modified nucleic acids, emission and electron paramagnetic resonance (EPR) spectroscopy for studying nucleic acid structure and dynamics, non-covalent binding of low- and high-MW ligands to nucleic acids and the design of unnatural base pairs. This unique book addresses new developments and is designed for graduate level and professional research purposes.

This book focuses on the regulation of transcription and translation in Archaea and arising insights into the evolution of RNA processing pathways. From synthesis to degradation and the implications of gene expression, it presents the current state of knowledge on archaeal RNA biology in 13 chapters. Topics covered include the modification and maturation of RNAs, the function of small non-coding RNAs and the CRISPR-Cas defense system. While Archaea have long been considered exotic microbial extremophiles, they are now increasingly being recognized as important model microorganisms for the study of molecular mechanisms conserved across the three domains of life, and with regard to the relevance of similarities and differences to eukaryotes and bacteria. This unique book offers a valuable resource for all readers interested in the regulation of gene expression in Archaea and RNA metabolism in general.

The origin of life is one of the biggest unsolved scientific questions. This book deals with the formation and first steps of the chemical evolution of nucleic acids, including the chemical roots behind the origin of their components from the simplest sources in a geochemical context. Chemical evolution encompasses the chemical processes and interactions conducive to self-assembly and supramolecular organization, leading to an increase of complexity and the emergence of life. The book starts with a personal account of the pioneering work of Stanley Miller and Jeffrey Bada on the Chemistry of Origins of Life and how the development of organic chemistry beginning in the 19th century led to the emergence of the field of prebiotic chemistry, situated at the frontier between organic, geo- and biochemistry. It then continues reviewing in tutorial manner current central topics regarding the organization of nucleic acids: the origin of nucleobases and nucleosides, their phosphorylation and polymerization and ultimately, their self-assembly and supramolecular organization at the inception of life.

The development of agents capable of cleaving RNA and DNA has attracted considerable attention from researchers in the last few years, because of the immediate and very important applications they can find in the emerging fields of biotechnology and pharmacology. There are essentially two classes of these agents - nucleases that occur naturally inside cells and synthetically produced artificial nucleases. The first class includes protein enzyme nucle­ ases and catalytic RNA structured ribozymes that perform cleavage of the phosphodiester bonds in nucleic acids according to a hydrolytic pathway in the course of different biochemical processes in the cell. A different pathway is used by some antibiotics which cleave DNA via redox-based mechanisms resulting in oxidative damage of nucleotide units and breakage of the DNA backbone. The above molecules are indispensable tools for manipulating nucleic acids and processing RNA; DNA-cleaving antibiotics and cytotoxic ribonucleases have demonstrated utility as chemotherapeutic agents. The second class, artificial nucleases, are rationally designed to imitate the active centers of natural enzymes by simple structures possessing minimal sets of the most important characteristics that are essential for catalysis. A dif­ ferent approach, in vitro selection, was also used to create artificial RNA and DNA enzymes capable of cleaving RNA. Being less efficient and specific as compared to the natural enzymes, the primitive mimics are smaller and robust and can function in a broad range of conditions.

Restriction enzymes are highly specific nucleases which occur ubiquitously among prokaryotic organisms, where they serve to protect bacterial cells against foreign DNA. Many different types of restriction enzymes are known, among them multi-subunit enzymes which depend on ATP or GTP hydrolysis for target site location. The best known representatives, the orthodox type II restriction endonucleases, are homodimers which recognize palindromic sequences, 4 to 8 base pairs in length, and cleave the DNA within or immediately adjacent to the recognition site. In addition to their important biological role (up to 10 % of the genomes of prokaryotic organisms code for restriction/modification systems!), they are among the most important enzymes used for the analysis and recombination of DNA. In addition, they are model systems for the study of protein-nucleic acids interactions and, because of their ubiquitous occurence, also for the understanding of the mechanisms of evolution.

The book is unique in that it bridges the gap between bioinformaticists and molecular biologists, i.e. the developers and the users of computational methods for biological data analysis and in that it presents examples of practical applications of the bioinformatics tools in the "daily practice" of an experimental research scientist. The book starts with reviews on computational methods for protein sequence-structure-function analysis (sequence studies, structure prediction), followed by methods that explicitly utilize experimental data routinely obtained in the laboratory to improve the functional predictions.The second part comprises a series of examples on how particular applications of different types of bioinformatics methods in combination with experimental studies to validate the hypotheses have led to important scientific discoveries. Therefore, the book is a guide to application of bioinformatics methods in molecular biology, addressed mainly to the research scientists, postdocs, and advanced graduate students.

This book provides the first and only comprehensive description and detailed summary of the genetics, structure, function, mechanisms of action, evolution and engineering of homing endonucleases and inteins. These two unique protein superfamilies, which are tied together through their frequent fusion and coevolution, have generated considerable excitement for their fundamental, structural, and functional properties, their evolution as parasitic elements, and their widespread applications as gene targeting agents and as instruments for the generation of modified proteins and novel protein combinations.

In recent years Molecular Biology has experienced an unprecedented revolution by the discovery of functional small RNAs. The number of cellular processes in which non-coding RNAs are involved is growing rapidly and include gene regulation on the transcriptional, post-transcriptional and translational level. To complicate matters, these processes seem to be strongly interconnected on the one hand, and diverse among different organisms on the other. This volume describes strategies for the discovery and validation of small RNAs and provides a snapshot of our current understanding of the different mechanisms triggered by small RNAs.

Mitochondrial DNA is one of the most explored genetic systems because of what it can tell us about the human past. This volume takes a unique perspective, presenting the disparate strands that must be tied together to exploit this system. From molecular biology to anthropology, statistics to ancient DNA, this first volume of three presents the global picture of human mitochondrial DNA variation. It takes a critical look at the field, flagging the problems, as well as the successes, and always placing the mitochondrial phylogeny centre stage.

Human neurological and neuromuscular disorders caused by nucleotide expansion, first discovered in 1991, are the focus of growing interest of practicing physicians and of interested biomedical researchers. This volume represents a comprehensive and up-to-date description of many of the better-studied disorders. The expert authors discuss molecular, clinical and pathological aspects of the diseases as well as our current understanding of their underlying mechanisms. Of special interest are ideas and initial results of the different therapeutic strategies that can be employed to overcome some of the disorders. As a summary of the state-of-the-art research in this field, this book is of value to human geneticists, molecular biologists and biochemists as well as to practicing neurologists and pediatricians.

In recent years, unprecedented advances in many aspects of the molecular biology of nucleic acids have been witnessed. The area of RNA chemistry has undergone a kind of explosion, with a huge interest in RNA-mediated catalysis. At the same time, our structural understanding of DNA-protein interactions has increased enormously, and the related area of RNA-protein interactions is beginning to gather pace. This softcover edition from the successful series Nucleic Acids and Molecular Biology is devoted to the structure and mechanism of ribozymes, and their potential exploitation. The subject has both important evolutionary implications and potential practical application in the development of therapeutic agents for diseases such as AIDS.

Site-specific mutagenesis of DNA, developed some thirty years ago, has proven to be one of the most important advances in biology. By allowing the site-specific replacement of any amino acid in a protein with one of the other nineteen amino acids, it ushered in the new era of "Protein Engineering". The field of protein engineering has, however, evolved rapidly since then and the last fifteen years have witnessed remarkable advances through the use of new chemical, biochemical and molecular biological tools towards the synthesis and manipulation of proteins. The chapters included in this book reflect the rapid evolution of protein engineering and its many applications in basic research, biotechnology, material sciences and therapy. This book will provide the reader with an introduction to state-of the-art concepts and methods and will be of use to anyone interested in the study of proteins, in academia as well as in industry.

“Editing a book on editing” has a certain “tongue in cheek” connotation to it, and I must admit that I was not aware what the job truly entailed when the project started. However, over the many months that it took to complete the book, it was interesting to realize that indeed “printing-type editing” and “biological editing” have many matching characteristics. Therefore, the quote by the well-known ? lm editor Verna Fields (1918–1982), “I wish the word “editing” had never been invented, “editing” implies correcting, and it’s not”, can function as a motto for the book: the various biological phenomena that are controlled by the different editing reactions are by far more complex than a simple correction process, and it is astounding how multifaceted the ? eld has become. All chapters of the book focus, as a general “editorial” subtext, on the corre- tion between RNA structure and function, and on complexity. This involves diff- ent length scales: from complex molecular machineries, to the interplay of complex biochemical pathways, and to evolutionary processes. The chapters are organized in a sequence beginning with a status quo account of RNA editing reactions from the focused perspective of RNA structure. This is followed by a chapter on the structure/function correlation in tRNA editing, and a chapter on RNA editing by adenosine deaminases that act on RNA (ADARs).

All living organisms are in a constant battle against their environment. Since uncontained microorganisms would simply overgrow all higher animals, the evolution of multicellular organisms required adequate and efficient defense mechanisms to protect their own integrity and to ensure their own survival. These defense mechanisms, encompassing receptor proteins that sense the presence of pathogens and effector molecules that are involved in controlling them, are the elemental parts of the innate immune system.For many species, the innate immune system is the sole active defense system. Long thought to be an unspecific immune response, the discovery of the Toll-like receptors and their ligands finally revealed just how specific the innate immune response actually is.This book wants to give an overview of our current knowledge about the innate immune system of plants, animals and humans. It not only covers the innate immune mechanisms and responses of so diverse organisms such as plants, Cnidaria, Drosophila, urochordates and zebrafish, but also the major receptor systems in mammalians and humans as well as the central defense mechanisms, antimicrobial peptides and the complement system.

This book presents applications of bioinformatics tools that experimental research scientists use in "daily practice". Its interdisciplinary approach combines computational and experimental methods to solve scientific problems. The book begins with reviews of computational methods for protein sequence-structure-function analysis, followed by methods that use experimental data obtained in the laboratory to improve functional predictions.

In recent years Molecular Biology has experienced an unprecedented revolution by the discovery of functional small RNAs. The number of cellular processes in which non-coding RNAs are involved is growing rapidly and include gene regulation on the transcriptional, post-transcriptional and translational level. To complicate matters, these processes seem to be strongly interconnected on the one hand, and diverse among different organisms on the other. This volume describes strategies for the discovery and validation of small RNAs and provides a snapshot of our current understanding of the different mechanisms triggered by small RNAs.