Download or read book Computational Characterization of Protein RNA Interactions and Implications for Phase Separation written by Alexandros Armaos and published by . This book was released on 2020 with total page 110 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite what was previously considered, the role of RNA is not only to carry the geneticinformation from DNA to proteins. Indeed, RNA has proven to be implicated in morecomplex cellular processes. Recent evidence suggests that transcripts have a regulatoryrole on gene expression and contribute to the spatial and temporal organization of theintracellular environment. They do so by interacting with RNA-binding proteins (RBPs)to form complex ribonucleoprotein (RNP) networks, however the key determinants thatgovern the formation of these complexes are still not well understood. In this work, I willdescribe algorithms that I developed to estimate the ability of RNAs to interact withproteins. Additionally, I will illustrate applications of computational methods to proposean alternative model for the function of Xist lncRNA and its protein network.Finally, I will show how computational predictions can be integrated with highthroughput approaches to elucidate the relationship between the structure of the RNA andits ability to interact with proteins. I conclude by discussing open questions and futureopportunities for computational analysis of cell's regulatory network.Overall, the underlying goal of my work is to provide biologists with new insights intothe functional association between RNAs and proteins as well as with sophisticated toolsthat will facilitate their investigation on the formation of RNP complexes.
Download or read book The Role of Protein Post Translational Modifications in Protein RNA Interactions and RNP Assemblies written by Roberto Giambruno and published by Frontiers Media SA. This book was released on 2022-02-11 with total page 123 pages. Available in PDF, EPUB and Kindle. Book excerpt: Dr. Nicolas Lux Fawzi is a member of the Scientific Advisory Board of Dewpoint Therapeutics LLC. All other Topic Editors declare no competing interests with regards to the Research Topic.
Download or read book I gruppi dirigenti in Europa occidentale tra dimensione nazionali e dimensioni sopranazionali written by and published by . This book was released on 1966 with total page 303 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Computational Analysis and Prediction of RNA protein Interactions written by Michael Uhl and published by . This book was released on 2022* with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Abstract: This dissertation is about the computational analysis and prediction of RNA-protein interactions. Ribonucleic acids (RNAs) and proteins both are essential for the control of gene expression in our cells. Gene expression is the process by which a functional gene product, namely a protein or an RNA, is produced from a gene, starting from the gene region on the DNA with the transcription of an RNA. Once regarded primarily as a messenger to transmit the protein information, recent years have seen RNA moving further into the biomedical spotlight, thanks to its increasingly uncovered roles in regulating gene expression. In addition, RNA has showcased its therapeutic potential, as famously demonstrated by the groundbreaking success of RNA vaccines in the COVID-19 pandemic. However, RNAs rarely function on their own: In humans, more than 1,500 different RNA-binding proteins (RBPs) are involved in controlling the various stages of an RNA's life cycle, creating a highly complex regulatory interplay between RNAs and proteins. It is therefore of fundamental importance to study these RNA-protein interactions, in order to deepen our understanding of gene expression. Over the last decade, CLIP-seq has become the dominant experimental method to identify the set of cellular RNA binding sites for an RBP of interest. However, analysing the resulting CLIP-seq data can be challenging, as there are many analysis steps and CLIP-seq protocol variants available, each requiring specific adaptations to the analysis workflow. Consequently, there is a need for analysis guidelines, providing easy access to tools, as well as the constant improvement of tools and workflows to increase the accuracy of the analysis results. The first set of works included in this thesis (publications P1, P4, and P5) deals with these topics, by providing a review article on CLIP-seq data analysis, as well as two articles on how to further improve CLIP-seq data analysis. Publication P1 supplies readers with an overview of tools and protocols, as well as guidelines to conduct a successful analysis, drawing largely from our own experience with analysing CLIP-seq data. Publication P4 demonstrates the issues current binding site identification tools have with CLIP-seq data from RBPs that bind to processed RNAs, and that the integration of RNA processing information improves the resulting binding site quality. On top of this, publication P5 presents Peakhood, the first tool that utilizes RNA processing information in order to increase the quality of RBP binding sites identified from CLIP-seq data. A natural drawback of experimental methods is that a target RNA needs to be sufficiently expressed in the observed cells for an RNA-protein interaction to be detected. Hence, since gene expression is a dynamic process that differs between cell types, time points, and conditions, a CLIP-seq experiment cannot recover the complete set of cellular RBP binding sites. This creates a demand for computational methods which can learn the binding properties of an RBP from existing CLIP-seq data, in order to predict RBP binding sites on any given target RNA. Besides interacting with proteins, RNAs can also interact with other RNAs, further increasing the amount of possible regulatory interactions between RNAs and proteins. In this regard, long non-coding RNAs (lncRNAs), a large class of non-protein-coding RNAs whose functions are still vastly unexplored, have become especially important, as it has been shown that they can engage in RNA-RNA interactions, whose regulatory mechanisms also include RNA-protein interactions. As such mechanistic studies are typically slow and expensive, computational tools that combine RNA-protein and RNA-RNA interaction predictions to infer potential mechanisms could be of great help, e.g., by screening a set of target RNAs and proteins and suggesting plausible mechanisms for experimental validation. The second set of works included in this thesis (publications P2 and P3) thus deals with the computational prediction of RNA-protein interactions, RNA-RNA interactions and the functional mechanisms that can be inferred from these interactions. Publication P2 introduces MechRNA, the first tool to infer functional mechanisms of lncRNAs based on their predicted interactions with RBPs and other RNAs, as well as gene expression data. We demonstrated MechRNA's capability to identify formerly described lncRNA mechanisms and experimentally validated one prediction, underlining its value for functional lncRNA studies. Finally, publication P3 presents RNAProt, a flexible and performant RBP binding site prediction tool based on recurrent neural networks. Compared to other popular deep learning methods, RNAProt achieves state-of-the-art predictive performance, as well as superior runtime efficiency. In addition, it is more feature-rich than any other available method, including the support of user-defined predictive features. We further showed that its visualizations agree with known RBP binding preferences, and demonstrated that its additional predictive features can increase the specificity of predictions
Download or read book Analyzing Microarray Gene Expression Data written by Geoffrey J. McLachlan and published by John Wiley & Sons. This book was released on 2005-02-18 with total page 366 pages. Available in PDF, EPUB and Kindle. Book excerpt: A multi-discipline, hands-on guide to microarray analysis of biological processes Analyzing Microarray Gene Expression Data provides a comprehensive review of available methodologies for the analysis of data derived from the latest DNA microarray technologies. Designed for biostatisticians entering the field of microarray analysis as well as biologists seeking to more effectively analyze their own experimental data, the text features a unique interdisciplinary approach and a combined academic and practical perspective that offers readers the most complete and applied coverage of the subject matter to date. Following a basic overview of the biological and technical principles behind microarray experimentation, the text provides a look at some of the most effective tools and procedures for achieving optimum reliability and reproducibility of research results, including: An in-depth account of the detection of genes that are differentially expressed across a number of classes of tissues Extensive coverage of both cluster analysis and discriminant analysis of microarray data and the growing applications of both methodologies A model-based approach to cluster analysis, with emphasis on the use of the EMMIX-GENE procedure for the clustering of tissue samples The latest data cleaning and normalization procedures The uses of microarray expression data for providing important prognostic information on the outcome of disease
Download or read book Computational Analysis of the Interplay Between RNA Structure and Function written by Elan A. Shatoff and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: RNA is ubiquitous in the cellular environment, and it can function in innumerable ways with a variety of interaction partners. A RNA molecule's structure, in particular the set of base pairing interactions between the nucleotides of the molecule known as secondary structure, can help determine its function. Since most proteins can only bind to either single stranded or double stranded RNA, RNA secondary structure can also help determine where and how RNA-protein binding interactions occur. In this work I investigate computational models for RNA-protein interactions in a variety of different contexts. In Chapter 2 I probe the effect of single nucleotide variations on RNA-protein binding as mediated by RNA secondary structure. Single nucleotide variations are single nucleotide changes in an organism's genome that can often cause disease, and may do so through a number of different mechanisms. In this work we propose that sequence changes can affect accessibility to protein binding sites through changes in secondary structure, even when these sequence changes occur tens of nucleotides outside of protein binding sites. We find that single nucleotide variations can have a many fold effect on the binding affinity of proteins for RNA, and characterize the genome-wide effect of single nucleotide variations on HuR binding. HuR is a single-stranded RNA binding protein that binds to AU-rich sequences, and has links to diseases such as cancer. We also find an asymmetry in this effect for HuR, indicating that this effect may be under selection. Following the previous work, which utilizes a model incorporating single stranded RNA binding proteins into RNA secondary structure folding, I introduce a model for incorporating double stranded RNA binding proteins (dsRBPs) into RNA secondary structure partition function calculations in Chapter 3. The dsRBPs are an important but understudied class of proteins that have uses in a wide range of processes. We implement our model in the ViennaRNA package, and validate it by calculating a number of experimental observables for transactivation response element RNA-binding protein. We find that RNA secondary structure can have a many fold effect on the effective binding affinity of dsRBPs, and show that calculated affinities for pre-miRNA-like constructs correlate with experimentally measured processing rates. Our model provides a novel method for interrogating the interplay between dsRBPs and RNA secondary structure. In Chapter 4 I study RNA-protein interactions in a different context, and investigate the role of Shine-Dalgarno (SD) sequences in translation in the Bacteroidetes. The Bacteroidetes are a phylum of bacteria known to rarely use SD sequences, but after performing a survey of SD usage in the phylum we find that certain ribosomal protein genes utilize them, particularly rpsU. A cryo-electron microscopy structure of the ribosome from Flavobacterium johnsoniae, a member of the Bacteroidetes, also shows that S21, which is encoded by the ribosomal open reading frame rpsU, sequesters the anti-Shine-Dalgarno (ASD) sequence. In our survey of SD sequences we also find covariation between the SD sequence of rpsU and the ASD sequence. These observations suggest an autoregulatory model for S21 in the Bacteroidetes.
Download or read book RNA Tagging written by Manfred Heinlein and published by Humana. This book was released on 2021-08-08 with total page 490 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a compendium of state-of-the-art methods for the labeling, detection, and purification of RNA and RNA-protein complexes and thereby constitutes an important toolbox for researchers interested in understanding the complex roles of RNA molecules in development, signaling, and disease. Beginning with a section on in situ detection of RNA molecules using FISH techniques, the volume continues with parts exploring in vivo imaging of RNA transport and localization, imaging and analysis of RNA uptake and transport between cells, identification and analysis of RNA-binding proteins, guide RNAs in genome editing, as well as other specific analytical techniques. Written for the highly successful Methods in Molecular Biology series, 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 practical, RNA Tagging: Methods and Protocols serves as a vital reference for researchers looking to further the increasingly important research in RNA biology.
Download or read book Characterization of RNA and RNA protein Complexes by Native Mass Spectrometry written by Samantha H. Sarni and published by . This book was released on 2020 with total page 175 pages. Available in PDF, EPUB and Kindle. Book excerpt: Protein-nucleic acid interactions are paramount for maintaining cellular homeostasis. Characterization of protein-nucleic acid complexes by high-resolution structural biology methods remains a challenge due to intrinsic structural and chemical heterogeneity. Native mass spectrometry (nMS) is a powerful bioanalytical tool for the investigation of proteins and protein complexes; however, it has only sparingly been implemented in the analysis of protein -nucleic acid complexes. This dissertation describes the application of native mass spectrometry to the analysis of RNA and RNA-protein complexes. Chapters 2 and 3 describe the characterization of the stoichiometry of the HIV-1 viral assembly nucleation complex. Using nMS, it was revealed that Gag specifically dimerizes in the presence of RNA containing the HIV-1 packaging signal (Psi), while other RNAs are bound primarily to monomeric Gag. Further investigations focused on the effect of transcription start site heterogeneity on the dimerization of the HIV-1 genomic RNA 5′ untranslated region (5′UTR), and stoichiometry. It was observed that 5′UTRs that begin with a single guanosine preferentially dimerize and are bound by Gag. Chapter 4 focuses on the characterization of a gas-phase separation method (ion mobility) as a structural biology tool for RNA. The effect of magnesium during RNA folding, solution temperature, ionization polarity, and collisional activation on the collision cross section of tRNAPhe were probed. It was observed that magnesium is essential for the folding and stability of tRNAPhe, consistent with previous reports. The collision cross sections (CCS) of tRNAPhe were compared in both positive and negative ionization polarities. The CCS of tRNAPhe refolded in under folding conditions was lower in negative mode relative to positive mode. It was observed that the CCS of WT tRNAPhe was not affected by the solution temperatures tested, however the CCS of a mutant (MT) tRNAPhe, that has a perturbed tertiary interaction network, increased as a function of solution temperature. Furthermore, we also probed the stability of these RNAs using collision-induced unfolding and it was observed that the wild-type RNA underwent collision-induced collapse while the mutant tRNA collapsed to a lesser extent. Lastly, a small dimeric RNA-RNA complex (HJ3) was used to determine whether RNA quaternary structure is preserved upon transfer to the gas phase. The intact dimer was observed in the gas-phase, and surface-induced dissociation was identified as an effective method for probing the stoichiometry and of RNA-RNA complexes. Chapter 5 describes the characterization of Hfq-RNA complex stability and subunit connectivity by surface-induced dissociation and ion mobility. It was observed that the intrinsically disordered C-terminal domains greatly stabilize Hfq. RNA-binding to Hfq destabilizes the wild-type protein yet stabilizes a protein that lacks C-terminal domains. The dissociation products observed for RNA-bound wild-type and the mutant Hfq were remarkably similar, suggesting that the C-terminal domains do not alter the RNA binding interfaces.
Download or read book Characterization of the Roles of Intrinsically Disordered Regions from RNA binding Proteins in Phase Separation written by Yuan Lin and published by . This book was released on 2016 with total page 113 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Biophysics of RNA Protein Interactions written by Chirlmin Joo and published by Springer Nature. This book was released on 2019-09-19 with total page 249 pages. Available in PDF, EPUB and Kindle. Book excerpt: RNA molecules play key roles in all aspects of cellular life, but to do so efficiently, they must work in synergism with proteins. This book addresses how proteins and RNA interact to carry out biological functions such as protein synthesis, regulation of gene expression, genome defense, liquid phase separation and more. The topics addressed in this volume will appeal to researchers in biophysics, biochemistry and structural biology. The book is a useful resource for anybody interested in elucidating the molecular mechanisms and discrete properties of RNA-protein complexes. Included are reviews of key systems such as microRNA and CRISPR/Cas that exemplify how RNA and proteins work together to perform their biological function. Also covered are techniques ranging from single molecule fluorescence and force spectroscopy to crystallography, cryo-EM microscopy, and kinetic modeling.
Download or read book RNA protein Interactions written by Kiyoshi Nagai and published by Oxford University Press, USA. This book was released on 1994 with total page 302 pages. Available in PDF, EPUB and Kindle. Book excerpt: The study of RNA-protein interactions is crucial to understanding the mechanisms and control of gene expression and protein synthesis. The realization that RNAs are often far more biologically active than was previously appreciated has stimulated a great deal of new research in this field. Uniquely, in this book, the world's leading researchers have collaborated to produce a comprehensive and current review of RNA-protein interactions for all scientists working in this area. Timely, comprehensive, and authoritative, this new Frontiers title will be invaluable for all researchers in molecular biology, biochemistry and structural biology.
Download or read book Molecular Theory of Capillarity written by J. S. Rowlinson and published by Courier Corporation. This book was released on 2013-04-26 with total page 354 pages. Available in PDF, EPUB and Kindle. Book excerpt: History of surface phenomena offers critical and detailed examination and assessment of modern theories, focusing on statistical mechanics and application of results in mean-field approximation to model systems. 1989 edition.
Download or read book Statistical Models written by David Freedman and published by Cambridge University Press. This book was released on 2009-04-27 with total page 442 pages. Available in PDF, EPUB and Kindle. Book excerpt: This lively and engaging book explains the things you have to know in order to read empirical papers in the social and health sciences, as well as the techniques you need to build statistical models of your own. The discussion in the book is organized around published studies, as are many of the exercises. Relevant journal articles are reprinted at the back of the book. Freedman makes a thorough appraisal of the statistical methods in these papers and in a variety of other examples. He illustrates the principles of modelling, and the pitfalls. The discussion shows you how to think about the critical issues - including the connection (or lack of it) between the statistical models and the real phenomena. The book is written for advanced undergraduates and beginning graduate students in statistics, as well as students and professionals in the social and health sciences.
Download or read book Advances in Protein Molecular and Structural Biology Methods written by Timir Tripathi and published by Academic Press. This book was released on 2022-01-14 with total page 716 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in Protein Molecular and Structural Biology Methods offers a complete overview of the latest tools and methods applicable to the study of proteins at the molecular and structural level. The book begins with sections exploring tools to optimize recombinant protein expression and biophysical techniques such as fluorescence spectroscopy, NMR, mass spectrometry, cryo-electron microscopy, and X-ray crystallography. It then moves towards computational approaches, considering structural bioinformatics, molecular dynamics simulations, and deep machine learning technologies. The book also covers methods applied to intrinsically disordered proteins (IDPs)followed by chapters on protein interaction networks, protein function, and protein design and engineering. It provides researchers with an extensive toolkit of methods and techniques to draw from when conducting their own experimental work, taking them from foundational concepts to practical application. Presents a thorough overview of the latest and emerging methods and technologies for protein study Explores biophysical techniques, including nuclear magnetic resonance, X-ray crystallography, and cryo-electron microscopy Includes computational and machine learning methods Features a section dedicated to tools and techniques specific to studying intrinsically disordered proteins
Download or read book Computational Structural Biology written by Torsten Schwede and published by World Scientific. This book was released on 2008 with total page 790 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is a comprehensive introduction to Landau-Lifshitz equations and Landau-Lifshitz-Maxwell equations, beginning with the work by Yulin Zhou and Boling Guo in the early 1980s and including most of the work done by this Chinese group led by Zhou and Guo since. The book focuses on aspects such as the existence of weak solutions in multi dimensions, existence and uniqueness of smooth solutions in one dimension, relations with harmonic map heat flows, partial regularity and long time behaviors. The book is a valuable reference book for those who are interested in partial differential equations, geometric analysis and mathematical physics. It may also be used as an advanced textbook by graduate students in these fields.
Download or read book Protein Self Assembly written by Jennifer J. McManus and published by Humana. This book was released on 2020-08-08 with total page 266 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume explores experimental and computational approaches to measuring the most widely studied protein assemblies, including condensed liquid phases, aggregates, and crystals. The chapters in this book are organized into three parts: Part One looks at the techniques used to measure protein-protein interactions and equilibrium protein phases in dilute and concentrated protein solutions; Part Two describes methods to measure kinetics of aggregation and to characterize the assembled state; and Part Three details several different computational approaches that are currently used to help researchers understand protein self-assembly. 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. Thorough and cutting-edge, Protein Self-Assembly: Methods and Protocols is a valuable resource for researchers who are interested in learning more about this developing field.
Download or read book Alternative Splicing and Disease written by Philippe Jeanteur and published by Springer Science & Business Media. This book was released on 2006-10-04 with total page 265 pages. Available in PDF, EPUB and Kindle. Book excerpt: Splicing of primary RNA transcript is a quasi-systematic step of gene expression in higher organisms. This is the first book to highlight the medical implications, i.e. diseases, caused by alternative splicing. Alternative splicing not only vastly increases protein diversity but also offers numerous opportunities for aberrant splicing events with pathological consequences. The book also outlines possible targets for therapy.
