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Author: Madeline Marie Mumbleau Publisher: ISBN: 9781658413633 Category : Languages : en Pages :
Book Description
RNA is considered one of the most versatile biological macromolecules, playing diverse roles in both encoding and manipulating gene expression. The function of RNA-mediated biology depends on the RNA's three-dimensional structure and its interactions with a multitude of biological ligands (proteins, small regulatory RNAs, and translation initiation or splice site selection machinery). One of these RNA-mediated pathways, RNA interference (RNAi), over the past two decades, has emerged a prominent tool and potential therapeutic utilizing small RNAs in regulating gene expression. Understanding the structure and function of these small RNAs, such as small interfering RNAs (siRNAs) is necessary to gain insight in the RNAi pathway. Building off of previous work in our laboratory, which demonstrated that chemically modifying siRNAs can lead to greater on-target selectivity and potency at guide position 6, we further explore the structural basis of this observation. We evaluated the structural impact of 7-ethynyl-8-aza-7-deazaadenosine (7-EAA) triazole modifications in RNA duplex formation and hAgo2-guide-target ternary complexes. A high-resolution crystal structure of an RNA duplex bearing a 7-EAA BrPh triazole suggests the ability to disrupt RNA-protein interactions. Leveraging off of successful results at guide position 6, initial studies with 7-EAA modified at a new guide position, guide position 7, were conducted to observe its influence of on-target potency and selectivity in the RNAi pathway. Both native and 7-EAA modified siRNAs at guide position 7 were tested to establish a preliminary understanding of how position-dependent modifications effect on-target and off-target knockdown efficiency. Initial results suggest that our target siRNA exhibits a potent IC50 for on-target knockdown experiments, whereas off-target knockdown was inconclusive. Hence, more experimental optimization is required to obtain more accurate and statistically significant results with 7-EAA and 7-EAA triazole modifications at siRNA guide position 7. Once optimized, further advances in rational siRNA therapeutic design can be achieved through the studies with 7-EAA modified siRNAs at guide position 7 and their effect on RNAi machinery.
Author: Madeline Marie Mumbleau Publisher: ISBN: 9781658413633 Category : Languages : en Pages :
Book Description
RNA is considered one of the most versatile biological macromolecules, playing diverse roles in both encoding and manipulating gene expression. The function of RNA-mediated biology depends on the RNA's three-dimensional structure and its interactions with a multitude of biological ligands (proteins, small regulatory RNAs, and translation initiation or splice site selection machinery). One of these RNA-mediated pathways, RNA interference (RNAi), over the past two decades, has emerged a prominent tool and potential therapeutic utilizing small RNAs in regulating gene expression. Understanding the structure and function of these small RNAs, such as small interfering RNAs (siRNAs) is necessary to gain insight in the RNAi pathway. Building off of previous work in our laboratory, which demonstrated that chemically modifying siRNAs can lead to greater on-target selectivity and potency at guide position 6, we further explore the structural basis of this observation. We evaluated the structural impact of 7-ethynyl-8-aza-7-deazaadenosine (7-EAA) triazole modifications in RNA duplex formation and hAgo2-guide-target ternary complexes. A high-resolution crystal structure of an RNA duplex bearing a 7-EAA BrPh triazole suggests the ability to disrupt RNA-protein interactions. Leveraging off of successful results at guide position 6, initial studies with 7-EAA modified at a new guide position, guide position 7, were conducted to observe its influence of on-target potency and selectivity in the RNAi pathway. Both native and 7-EAA modified siRNAs at guide position 7 were tested to establish a preliminary understanding of how position-dependent modifications effect on-target and off-target knockdown efficiency. Initial results suggest that our target siRNA exhibits a potent IC50 for on-target knockdown experiments, whereas off-target knockdown was inconclusive. Hence, more experimental optimization is required to obtain more accurate and statistically significant results with 7-EAA and 7-EAA triazole modifications at siRNA guide position 7. Once optimized, further advances in rational siRNA therapeutic design can be achieved through the studies with 7-EAA modified siRNAs at guide position 7 and their effect on RNAi machinery.
Author: Kazuhiko Nakatani Publisher: Springer ISBN: 3319271113 Category : Science Languages : en Pages : 280
Book Description
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.
Author: Imre Gaspar Publisher: Humana Press ISBN: 9781493972128 Category : Medical Languages : en Pages : 492
Book Description
This volume introduces different concepts and methods of detecting RNA in biological material in a variety of model systems. The chapters in this book discuss methods that will answer numerous biological questions that arise in the study of RNAs. Some of the topics covered in this book are single mRNA molecule detection in embryos and neurons; detection of mRNA and associated molecules by ISH-IEM on frozen sections; optimizing molecular beacons for intracellular analysis of RNA; imaging translation dynamics of single mRNA molecules in live cells; preparation of high-throughput sequencing libraries; and capturing RNA binding proteins in embryos and in cell-culture. 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. Cutting-edge and comprehensive, RNA Detection: Methods and Protocols is a valuable resource for novel and experiences scientist in the expanding field of RNAs.
Author: G Michael Blackburn Publisher: Royal Society of Chemistry ISBN: 1782625771 Category : Science Languages : en Pages : 503
Book Description
The structure, function and reactions of nucleic acids are central to molecular biology and are crucial for the understanding of complex biological processes involved. Revised and updated Nucleic Acids in Chemistry and Biology 3rd Edition discusses in detail, both the chemistry and biology of nucleic acids and brings RNA into parity with DNA. Written by leading experts, with extensive teaching experience, this new edition provides some updated and expanded coverage of nucleic acid chemistry, reactions and interactions with proteins and drugs. A brief history of the discovery of nucleic acids is followed by a molecularly based introduction to the structure and biological roles of DNA and RNA. Key chapters are devoted to the chemical synthesis of nucleosides and nucleotides, oligonucleotides and their analogues and to analytical techniques applied to nucleic acids. The text is supported by an extensive list of references, making it a definitive reference source. This authoritative book presents topics in an integrated manner and readable style. It is ideal for graduate and undergraduates students of chemistry and biochemistry, as well as new researchers to the field.
Author: Henri Grosjean Publisher: CRC Press ISBN: 1498713157 Category : Science Languages : en Pages : 682
Book Description
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 shortconclusion and future prospect' section and
Author: Bin Wang Publisher: CRC Press ISBN: 9814411647 Category : Medical Languages : en Pages : 468
Book Description
In the past few decades there has been incredible growth in "bionano"-related research, which has been accompanied by numerous publications in this field. Although various compilations address topics related to deoxyribonucleic acid (DNA) and protein, there are few books that focus on determining the structure of ribonucleic acid (RNA) and using RNA as building blocks to construct nanoarchitectures for biomedical and healthcare applications. RNA Nanotechnology is a comprehensive volume that details both the traditional approaches and the latest developments in the field of RNA-related technology. This book targets a wide audience: a broad introduction provides a solid academic background for students, researchers, and scientists who are unfamiliar with the subject, while the in-depth descriptions and discussions are useful for advanced professionals. The book opens with reviews on the basic aspects of RNA biology, computational approaches for predicting RNA structures, and traditional and emerging experimental approaches for probing RNA structures. This section is followed by explorations of the latest research and discoveries in RNA nanotechnology, including the design and construction of RNA-based nanostructures. The final segment of the book includes descriptions and discussions of the potential biological and therapeutic applications of small RNA molecules, such as small/short interfering RNAs (siRNAs), microRNAs (miRNAs), RNA aptamers, and ribozymes.
Author: Serge L. Beaucage Publisher: Current Protocols ISBN: 9780471246626 Category : Science Languages : en Pages :
Book Description
Good methods must be reliable, well-tested, and honed to minimize the time and expense required to achieve the desired results. CPNC provides a continuously growing and evolving set of protocols that allows researchers to benefit from the experience of other researchers around the world. The core manual provides a comprehensive set of protocols that have been compiled, revised, and streamlined over the last 6 years. Quarterly updates provide new protocols in emerging areas of research as well as continued advances and new applications for fundamental methods. The book is designed to grow and change with the field of nucleic acid chemistry. Fundamental nucleoside chemistry methods include sugar-base condensation, phosphorylation, and nucleoside protection. Methods for oligonucleotide synthesis include H-phosphonate and phosphoramidite approaches, solid-phase and solution-phase synthesis, large-scale synthesis, synthesis for modified and unmodified oligonucleotides, conjugation of oligonucleotides, synthesis without base protection, and synthesis on microarrays. More specialized synthetic methods include synthesis of biologically active nucleosides and prodrugs. Purification and characterization methods are detailed. Advanced methods include biophysical analysis, combinatorial methods, and nanotechnology. Each protocol includes rationale for choosing appropriate methods, step-by-step procedures, complete recipes, anticipated results, characterization data, and troubleshooting, as well as background and recommended reading. The level of procedural detail is far beyond that found in the research literature, and tips and comments from authors are geared towards ensuring reliable duplication in the laboratory.
Author: Antonello Mai Publisher: Springer Nature ISBN: 3030429822 Category : Science Languages : en Pages : 569
Book Description
This book presents an authoritative review of the most significant findings about all the epigenetic targets (writers, readers, and erasers) and their implication in physiology and pathology. The book also covers the design, synthesis and biological validation of epigenetic chemical modulators, which can be useful as novel chemotherapeutic agents. Particular attention is given to the chemical mechanisms of action of these molecules and to the drug discovery prose which allows their identification. This book will appeal to students who want to know the extensive progresses made by epigenetics (targets and modulators) in the last years from the beginning, and to specialized scientists who need an instrument to quickly search and check historical and/or updated notices about epigenetics.
Author: Madeline Marie Mumbleau
Author: Madeline Marie Mumbleau
Author: Kazuhiko Nakatani
Author: Imre Gaspar
Author: G Michael Blackburn
Author: 
Author: Henri Grosjean
Author: Bin Wang
Author: Mahesh Uttamchandani
Author: Serge L. Beaucage
Author: Antonello Mai