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Algorithms and Analysis of Inter-and Intra-molecular RNA Base Pair Interaction Networks

Algorithms and Analysis of Inter-and Intra-molecular RNA Base Pair Interaction Networks
Author: Antoine Soulé
Publisher:
Total Pages:
Release: 2020
Genre:
ISBN:

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"Ribonucleic acids (RNAs) are central molecules of cellular biology, present in all known living organisms. RNAs fulfill a wide range of essential biological functions, many of those requiring the linear RNAs to fold into complex three-dimensional structures. The folding of RNAs, as well as the interactions between RNAs molecule, are driven by chemical interactions between pairs of nucleotides called base pairs. The sets of base pairs interactions stabilize the molecules and coerce their conformation in intricate ways. Canonical base pairs are bound by two to three hydrogen bonds and are the most stable base pairs. However, the main contribution to the molecule stability comes from the stacking of adjacent base pairs into stems. Moreover, nu- cleotides may also form non-canonical base pairs, and riboses as well as phosphate groups may also form hydrogen bonds. As the stems are very stable, the remaining regions, called loops, are preferential sites for interactions between distant portions of the molecule or between distinct RNA molecules. Non-canonical base pairs structure those loops and are also often involved in those long-range interactions. As a consequence, non-canonical base pairs are highly involved in the functions of RNAs.In this thesis, we explore the complexity of RNA base pair interaction networks, both at the intra-molecular and inter-molecular levels. In order to do so, we develop new algorithms and methods relying on graph matching and machine learning to extract patterns and signal from RNA structures and sequences but also to organize an analyze our results.This thesis paves the way towards a better understanding of the intricate intra-molecular RNA base pairs networks, especially the ones involving non-canonical base pairs, and their contribu- tion to RNA structure both by studying some of them and by providing tools to produce new studies. This thesis also opens up new perspectives on the organization of RNAs and, more specifically, on the influence of inter-molecular interactions on the RNA sequences at a cellular level"--


RNA-RNA Interactions

RNA-RNA Interactions
Author: Frank J. Schmidt
Publisher: Humana Press
Total Pages: 0
Release: 2014-10-29
Genre: Medical
ISBN: 9781493918959

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In this volume expert researchers in the field detail many of the methods which are now commonly used to study RNA. These methods are presented as a guidebook to scientists who are experienced with RNA research and want to brush up on a new technique. 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 key tips on troubleshooting and avoiding known pitfalls. Thorough and intuitive, RNA-RNA Interactions: Methods and Protocols guides scientists investigating biological systems and studying RNA.


Global Analysis of the Human RNA-RNA Interactome

Global Analysis of the Human RNA-RNA Interactome
Author: Eesha Sharma
Publisher:
Total Pages: 0
Release: 2019
Genre:
ISBN:

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Numerous characterized non-coding (nc)RNAs function via base-pairing with target RNAs to direct essential roles in RNA processing, modification, turnover and translation. Moreover, functionally important RNA-RNA interactions have been defined in precursor (pre)-mRNA and spliced mRNAs. These previous studies therefore suggested that many additional important RNA-RNA interactions remain to be discovered and characterized. A major challenge in the field of RNA biology is therefore to systematically identify and characterize functionally important RNA-RNA interactions. Computational methods have yielded limited success, and previously there was a lack of global-scale experimental approaches to address this challenge. Accordingly, I developed and applied LIGR-Seq, a new method that enables the global-scale mapping of RNA-RNA interactions. LIGR-Seq involves cross-linking of RNA duplexes in cells and, following cell lysis and partial digestion and ligation of interacting RNA, high-throughput sequencing and mapping of the RNA ligation products to define RNA-RNA interactions. I used LIGR-Seq to map known and new ncRNA-mRNA interactions in human cells. These data led to the discovery that specific snoRNAs function in the regulation of turnover of target mRNAs, in addition to their well-established canonical roles in RNA modifications. I next developed and applied an 'enhanced' (e)LIGR-Seq protocol that affords more sensitive detection of RNA-RNA interactions. eLIGR-Seq data revealed a previously unknown RNA structure in primary transcripts encoding the small ribosomal protein subunit RPS26 that functions in its negative auto-regulation. Characterization of this and a competing RNA structure revealed that RPS26 protein functions in negative feedback regulation by binding and stabilizing a structure in its pre-mRNA that favours the formation of a non-expressed, circular RNA variant, over the corresponding, expressed linear mRNA. This finding thus represents a new function for RNA structure and circular isoforms. It further has implications for understanding Diamond-Blackfan anemias associated with mutations in RPS26. In summary, my thesis research has contributed a valuable method that has enabled the discovery and characterization of RNA-RNA interactomes. The results from this work are providing new insight into the roles of the myriad of uncharacterized inter- and intramolecular RNA-RNA interactions that underlie critical biological functions.


RNA 3D Structure Analysis and Prediction

RNA 3D Structure Analysis and Prediction
Author: Neocles Leontis
Publisher: Springer Science & Business Media
Total Pages: 402
Release: 2012-06-05
Genre: Science
ISBN: 3642257402

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With the dramatic increase in RNA 3D structure determination in recent years, we now know that RNA molecules are highly structured. Moreover, knowledge of RNA 3D structures has proven crucial for understanding in atomic detail how they carry out their biological functions. Because of the huge number of potentially important RNA molecules in biology, many more than can be studied experimentally, we need theoretical approaches for predicting 3D structures on the basis of sequences alone. This volume provides a comprehensive overview of current progress in the field by leading practitioners employing a variety of methods to model RNA 3D structures by homology, by fragment assembly, and by de novo energy and knowledge-based approaches.


RNA Biochemistry and Biotechnology

RNA Biochemistry and Biotechnology
Author: Jan Barciszewski
Publisher: Springer Science & Business Media
Total Pages: 373
Release: 2012-12-06
Genre: Science
ISBN: 9401144850

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RNA Biochemistry and Biotechnology describes various aspects of nucleic acid and protein structure, mainly RNA structure and proteins, interacting with specific RNA species. Papers deal with DNA protein interactions, telomerase, aminoacyl-tRNA synthetases, elongation factor Tu, DNA repair, RNA structure, NMR technology, RNA aptamer interaction of biological macromolecules with metal ions. Two papers deal with theoretical aspects of RNA structure production and computer modelling. Many papers describe the possibility of commercial application of RNA biotechnology. One article discusses the impact of direct democracy on basic science supporting biotechnology. Readership: Advanced graduate students, Ph.D. students and young scientists as well as specialists in the field.


RNA Sequence, Structure, and Function: Computational and Bioinformatic Methods

RNA Sequence, Structure, and Function: Computational and Bioinformatic Methods
Author: Jan Gorodkin
Publisher: Humana
Total Pages: 0
Release: 2014-03-18
Genre: Science
ISBN: 9781627037082

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The existence of genes for RNA molecules not coding for proteins (ncRNAs) has been recognized since the 1950's, but until recently, aside from the critically important ribosomal and transfer RNA genes, most focus has been on protein coding genes. However, a long series of striking discoveries, from RNA's ability to carry out catalytic function, to discovery of riboswitches, microRNAs and other ribo-regulators performing critical tasks in essentially all living organisms, has created a burgeoning interest in this primordial component of the biosphere. However, the structural characteristics and evolutionary constraints on RNA molecules are very different from those of proteins, necessitating development of a completely new suite of informatic tools to address these challenges. In RNA Sequence, Structure, Function: Computational and Bioinformatic Methods, expert researchers in the field describe a substantial and relevant fraction of these methodologies from both practical and computational/algorithmic perspectives. Focusing on both of these directions addresses both the biologist interested in knowing more about RNA bioinformatics as well as the bioinformaticist interested in more detailed aspects of the algorithms. Written in the highly successful Methods in Molecular Biology series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results. Thorough and intuitive, RNA Sequence, Structure, Function: Computational and Bioinformatic Methods aids scientists in continuing to study key methods and principles of RNA bioinformatics.


Protein-protein Complexes

Protein-protein Complexes
Author: Martin Zacharias
Publisher: World Scientific
Total Pages: 401
Release: 2010
Genre: Science
ISBN: 1848163398

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Given the immense progress achieved in elucidating protein-protein complex structures and in the field of protein interaction modeling, there is great demand for a book that gives interested researchers/students a comprehensive overview of the field. This book does just that. It focuses on what can be learned about protein-protein interactions from the analysis of protein-protein complex structures and interfaces. What are the driving forces for protein-protein association? How can we extract the mechanism of specific recognition from studying protein-protein interfaces? How can this knowledge be used to predict and design protein-protein interactions (interaction regions and complex structures)? What methods are currently employed to design protein-protein interactions, and how can we influence protein-protein interactions by mutagenesis and small-molecule drugs or peptide mimetics?The book consists of about 15 review chapters, written by experts, on the characterization of protein-protein interfaces, structure determination of protein complexes (by NMR and X-ray), theory of protein-protein binding, dynamics of protein interfaces, bioinformatics methods to predict interaction regions, and prediction of protein-protein complex structures (docking and homology modeling of complexes, etc.) and design of protein-protein interactions. It serves as a bridge between studying/analyzing protein-protein complex structures (interfaces), predicting interactions, and influencing/designing interactions.


Gene Quantification

Gene Quantification
Author: Francois Ferre
Publisher: Springer Science & Business Media
Total Pages: 379
Release: 2012-12-06
Genre: Medical
ISBN: 1461241642

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Geneticists and molecular biologists have been interested in quantifying genes and their products for many years and for various reasons (Bishop, 1974). Early molecular methods were based on molecular hybridization, and were devised shortly after Marmur and Doty (1961) first showed that denaturation of the double helix could be reversed - that the process of molecular reassociation was exquisitely sequence dependent. Gillespie and Spiegelman (1965) developed a way of using the method to titrate the number of copies of a probe within a target sequence in which the target sequence was fixed to a membrane support prior to hybridization with the probe - typically a RNA. Thus, this was a precursor to many of the methods still in use, and indeed under development, today. Early examples of the application of these methods included the measurement of the copy numbers in gene families such as the ribosomal genes and the immunoglo bulin family. Amplification of genes in tumors and in response to drug treatment was discovered by this method. In the same period, methods were invented for estimating gene num bers based on the kinetics of the reassociation process - the so-called Cot analysis. This method, which exploits the dependence of the rate of reassociation on the concentration of the two strands, revealed the presence of repeated sequences in the DNA of higher eukaryotes (Britten and Kohne, 1968). An adaptation to RNA, Rot analysis (Melli and Bishop, 1969), was used to measure the abundance of RNAs in a mixed population.


Solvation Thermodynamics

Solvation Thermodynamics
Author: Arieh Y. Ben-Naim
Publisher: Springer Science & Business Media
Total Pages: 253
Release: 2013-03-09
Genre: Science
ISBN: 1475765509

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This book deals with a subject that has been studied since the beginning of physical chemistry. Despite the thousands of articles and scores of books devoted to solvation thermodynamics, I feel that some fundamen tal and well-established concepts underlying the traditional approach to this subject are not satisfactory and need revision. The main reason for this need is that solvation thermodynamics has traditionally been treated in the context of classical (macroscopic) ther modynamics alone. However, solvation is inherently a molecular pro cess, dependent upon local rather than macroscopic properties of the system. Therefore, the starting point should be based on statistical mechanical methods. For many years it has been believed that certain thermodynamic quantities, such as the standard free energy (or enthalpy or entropy) of solution, may be used as measures of the corresponding functions of solvation of a given solute in a given solvent. I first challenged this notion in a paper published in 1978 based on analysis at the molecular level. During the past ten years, I have introduced several new quantities which, in my opinion, should replace the conventional measures of solvation thermodynamics. To avoid confusing the new quantities with those referred to conventionally in the literature as standard quantities of solvation, I called these "nonconventional," "generalized," and "local" standard quantities and attempted to point out the advantages of these new quantities over the conventional ones.


Principles of Nucleic Acid Structure

Principles of Nucleic Acid Structure
Author: Wolfram Saenger
Publisher: Springer Science & Business Media
Total Pages: 574
Release: 2013-12-01
Genre: Science
ISBN: 1461251907

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New textbooks at all levels of chemistry appear with great regularity. Some fields like basic biochemistry, organic reaction mechanisms, and chemical ther modynamics are well represented by many excellent texts, and new or revised editions are published sufficiently often to keep up with progress in research. However, some areas of chemistry, especially many of those taught at the grad uate level, suffer from a real lack of up-to-date textbooks. The most serious needs occur in fields that are rapidly changing. Textbooks in these subjects usually have to be written by scientists actually involved in the research which is advancing the field. It is not often easy to persuade such individuals to set time aside to help spread the knowledge they have accumulated. Our goal, in this series, is to pinpoint areas of chemistry where recent progress has outpaced what is covered in any available textbooks, and then seek out and persuade experts in these fields to produce relatively concise but instructive introductions to their fields. These should serve the needs of one semester or one quarter graduate courses in chemistry and biochemistry. In some cases the availability of texts in active research areas should help stimulate the creation of new courses. CHARLES R. CANTOR New York Preface This monograph is based on a review on polynucleotide structures written for a book series in 1976.