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Recent studies in human genetics and in silico analyses have revealed that a number of genes are head-head orientated with other genes or non-coding RNAs. The expression of regulatory element-containing 5'-upstream regions of gene pairs are referred to as bi-directional promoters and are thought to have a key role in biological regulatory mechanisms. For example, tumor suppressor protein-encoding TP53 and BRCA1 genes are head-head bound with WRAP53 and NBR2, respectively. DNA-repair factor-encoding ATM and PRKDC (DNA-PKcs) genes have bidirectional partner NPAT and MCM4, respectively. Surveillance of the human DNA database has revealed that the numbers of DNA repair/mitochondrial function/immune response-associated genes are bound with other genes that are transcribed to opposite direction. The observations may encourage us to investigate in the molecular mechanisms how DNA repair/mitochondrial function/immune response-associated genes are regulated by bidirectional promoters. Not only protein-coding genes, but also quite a few ncRNAs, which play important roles in various cellular events, are transcribed under the regulation of the bidirectional promoters. More importantly, we know that dysregulation in the promoter activity and transcription initiation of genes might cause human diseases. - Provides an overview of the process of transcription - Explains why there so many bidirectional promoters present in human genomes - Covers how the diverse biological functions of (non-coding RNAs) ncRNAs are controlled
The diversity of RNAs inside living cells is amazing. We have known of the more “classic” RNA species: mRNA, tRNA, rRNA, snRNA and snoRNA for some time now, but in a steady stream new types of molecules are being described as it is becoming clear that most of the genomic information of cells ends up in RNA. To deal with the enormous load of resulting RNA processing and degradation reactions, cells need adequate and efficient molecular machines. The RNA exosome is arising as a major facilitator to this effect. Structural and functional data gathered over the last decade have illustrated the biochemical importance of this multimeric complex and its many co-factors, revealing its enormous regulatory power. By gathering some of the most prominent researchers in the exosome field, it is the aim of this volume to introduce this fascinating protein complex as well as to give a timely and rich account of its many functions. The exosome was discovered more than a decade ago by Phil Mitchell and David Tollervey by its ability to trim the 3’end of yeast, S. cerevisiae, 5. 8S rRNA. In a historic account they laid out the events surrounding this identification and the subsequent birth of the research field. In the chapter by Kurt Januszyk and Christopher Lima the structural organization of eukaryotic exosomes and their evolutionary counterparts in bacteria and archaea are discussed in large part through presentation of structures.
Mitochondria are far more than the “powerhouse” of the cell as they have classically been described. In fact, mitochondria biological activities have progressively expanded to include not only various bioenergetic processes but also important biosynthetic pathways, calcium homeostasis and thermogenesis, cell death by apoptosis, several different signal transduction pathways mainly related to redox control of gene expression and so on. This functional and structural complexity may undergo important derangements so to justify the definition of ‘mitochondrial medicine’, which should include all the clinical consequences of congenital or acquired mitochondrial dysfunctions. There are actually a growing number of studies which assign a significant pathogenic role to damaged mitochondria in different diseases: ischemia/reperfusion injury, neurodegenerative diseases, cancer with its dramatic sequelae (i.e, metastasis), metabolic syndrome, hyperlipidemias, just to mention a few of the most important pathologies. In this context, a further aspect that should not be disregarded is the interaction of pharmacological agents with mitochondria, not only in regard of the toxicological aspects but, above all, of the potential therapeutic applications. In fact, it is interesting to note that, while the properties of different so-called “mitoxicants” are well-known, the subtle linkages between drugs and mitochondria is still in need of a real pharmacological and therapeutic control at the clinical level. This lack of consideration can often lead to an underestimation of unwanted toxic effects but also of desirable therapeutic activities. A reevaluation of the potential clinical role of mitochondria could give a new light on some yet obscure aspects of human pathophysiology.
This volume contains cutting-edge techniques to study the function of enhancers and promoters in depth. Chapters are divided into six sections and describe enhancer-promoter transcripts, nucleosome occupancy, DNA accessibility, chromatin interactions, protein-DNA interactions, functional analyses, and DNA methylation assays. Written in the Methods in Molecular Biology series format, chapters include comprehensive introductions, lists of the necessary materials and reagents, step-by-step laboratory protocols, and useful suggestions for troubleshooting. Authoritative and cutting-edge, Enhancers and Promoters: Methods and Protocols is a useful guide for future experiments.
Now in its fifth edition and for the first time available as an electronic product with all entries cross-linked. This very successful long-seller has once again been thoroughly updated and greatly expanded. It now contains over 13,000 entries, and comprehensively covering genomics, transcriptomics, and proteomics. Each entry contains an extensive explanation, including a comprehensive listing of synonyms and acronyms, and all formulas have been redrawn to create a uniform style, while most of the figures are custom designed for this dictionary. The ultimate reference for all terms in the -omics fields.
Presents the principles of human gene evolution in a concise and easy to understand fashion. Uses examples of how evolutionary processes have molded present day genes, drawn from the evolution of humans and other primates, as well as from more primitive organisms. With increasing attention in this expanding area, this review forms a timely publication of our current knowledge of this important field. Structure and function in the human genome The evolution of gene structure Mutational mechanisms in evolution
The control of plant gene expression at the transcriptional level is the main subject of this volume. Genetics, molecular biology and gene technology have dramatically improved our knowledge of this event. The functional analysis of promoters and transcription factors provides more and more insights into the molecular anatomy of initiation complexes assembled from RNA polymerase and the multiplicity of helper and control proteins. Formation of specific DNA-protein complexes - activating or repressing transcription - is the crux of developmental or environmental control of gene expression. The book presents an up-to-date, critical overview of this rapidly advancing field.
This comprehensive account of the human herpesviruses provides an encyclopedic overview of their basic virology and clinical manifestations. This group of viruses includes human simplex type 1 and 2, Epstein–Barr virus, Kaposi's Sarcoma-associated herpesvirus, cytomegalovirus, HHV6A, 6B and 7, and varicella-zoster virus. The viral diseases and cancers they cause are significant and often recurrent. Their prevalence in the developed world accounts for a major burden of disease, and as a result there is a great deal of research into the pathophysiology of infection and immunobiology. Another important area covered within this volume concerns antiviral therapy and the development of vaccines. All these aspects are covered in depth, both scientifically and in terms of clinical guidelines for patient care. The text is illustrated generously throughout and is fully referenced to the latest research and developments.
This topic focuses on distribution, synthesis, metabolism, and the in vivo roles of melatonin in plants, with 1 editorial, 3 reviews, 21 original research studies and 1 corrigendum.
This book edition is intended to provide a concise summary for select topics in DNA repair, a field that is ever-expanding in complexity and biologic significance. The topics reviewed ranged from fundamental mechanisms of DNA repair to the interface between DNA repair and a spectrum on cellular process to the clinical relevance of DNA repair in oncologic paradigms. The information in this text should provide a foundation from which one can explore the various topics in depth. The book serve as a supplementary text in seminar courses with focus on DNA repair as well as a general reference for scholars with an interest in DNA repair.