Download or read book RNA Motifs and Regulatory Elements written by Peter Bengert and published by Springer Science & Business Media. This book was released on 2002 with total page 248 pages. Available in PDF, EPUB and Kindle. Book excerpt: RNA Motifs and Regulatory Elements is the new edition of the successful book, "Regulatory RNA". It alerts the reader to the importance of regulatory RNA elements for the many different areas of cellular life.The computational and experimental methods and tools to search for new interesting regulatory RNA structures are explained and compared. The knowledge on regulatory RNA structures and elements already available is concisely summarized as well as catalogued. In addition, interesting RNA elements are analyzed in detail regarding their dynamics, regulation, and as a dominant topic of current resarch in molecular biology, including areas such as RNA mediated regulation of gene-expression, DNA/RNA chip data, and ribozymes, splicing, or telomerases in aging. Medical implications are also covered. Future progress and research are finally outlined.

Download or read book Regulatory RNA written by Thomas Dandekar and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 270 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides an introduction to and an overview of the field of regulatory RNA, focusing on the identification of regulatory elements and motifs in such RNA molecules. Central to the book is the use of appropriate techniques to identify regulatory RNA and regulatory motifs. The prospects for this new and expanding research field - understanding regulatory RNA elements and motifs - are also explored, including new developments, medical applications, and applications in other fields.

Download or read book RNA Motifs and Regulatory Elements written by Thomas Dandekar and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 234 pages. Available in PDF, EPUB and Kindle. Book excerpt: RNA Motifs and Regulatory Elements is the new edition of the successful book, "Regulatory RNA". It alerts the reader to the importance of regulatory RNA elements for the many different areas of cellular life. The computational and experimental methods and tools to search for new interesting regulatory RNA structures are explained and compared. The knowledge on regulatory RNA structures and elements already available is concisely summarized as well as catalogued. In addition, interesting RNA elements are analyzed in detail regarding their dynamics, regulation, and as a dominant topic of current resarch in molecular biology, including areas such as RNA mediated regulation of gene-expression, DNA/RNA chip data, and ribozymes, splicing, or telomerases in aging. Medical implications are also covered. Future progress and research are finally outlined.

Download or read book The Analysis of Regulatory DNA Current Developments Knowledge and Applications Uncovering Gene Regulation written by Kenneth Berendzen and published by Bentham Science Publishers. This book was released on 2013-10-29 with total page 225 pages. Available in PDF, EPUB and Kindle. Book excerpt: A major goal of integrative research is understanding regulatory networks to such an extent as to allow researchers to model developmental and stress responses. Regulatory networks of living systems include complex and vast interactions between proteins, metabolites, RNA, various signaling molecules and DNA. One aspect of systems biology is understanding the dynamics of protein-DNA interactions affecting gene expression that are caused by transcription factors (TFs) and chromatin remodeling factors. This e-book provides a resource for summarizing current knowledge eukaryotic transcription and explores cis-elements and methods for their analysis, prediction and discovery. The book also presents an overview of exploring gene regulatory networks, chromatin, and miRNAs. Information about state-of-the-art techniques for the determination of TF - cis-element interactions in vivo and in silico give cutting edge insights on how genomic-scale research is being approached. The Analysis of Regulatory DNA provides readers with both the necessary background knowledge and provocative, up-to-date insights aimed at sparking new and vibrant experimental designs for understanding and predicting cis-elements in the eukaryotic genome.

Download or read book Computational Genomics with R written by Altuna Akalin and published by CRC Press. This book was released on 2020-12-16 with total page 462 pages. Available in PDF, EPUB and Kindle. Book excerpt: Computational Genomics with R provides a starting point for beginners in genomic data analysis and also guides more advanced practitioners to sophisticated data analysis techniques in genomics. The book covers topics from R programming, to machine learning and statistics, to the latest genomic data analysis techniques. The text provides accessible information and explanations, always with the genomics context in the background. This also contains practical and well-documented examples in R so readers can analyze their data by simply reusing the code presented. As the field of computational genomics is interdisciplinary, it requires different starting points for people with different backgrounds. For example, a biologist might skip sections on basic genome biology and start with R programming, whereas a computer scientist might want to start with genome biology. After reading: You will have the basics of R and be able to dive right into specialized uses of R for computational genomics such as using Bioconductor packages. You will be familiar with statistics, supervised and unsupervised learning techniques that are important in data modeling, and exploratory analysis of high-dimensional data. You will understand genomic intervals and operations on them that are used for tasks such as aligned read counting and genomic feature annotation. You will know the basics of processing and quality checking high-throughput sequencing data. You will be able to do sequence analysis, such as calculating GC content for parts of a genome or finding transcription factor binding sites. You will know about visualization techniques used in genomics, such as heatmaps, meta-gene plots, and genomic track visualization. You will be familiar with analysis of different high-throughput sequencing data sets, such as RNA-seq, ChIP-seq, and BS-seq. You will know basic techniques for integrating and interpreting multi-omics datasets. Altuna Akalin is a group leader and head of the Bioinformatics and Omics Data Science Platform at the Berlin Institute of Medical Systems Biology, Max Delbrück Center, Berlin. He has been developing computational methods for analyzing and integrating large-scale genomics data sets since 2002. He has published an extensive body of work in this area. The framework for this book grew out of the yearly computational genomics courses he has been organizing and teaching since 2015.

Download or read book Post Transcriptional Gene Regulation written by Jeffrey Wilusz and published by Springer Science & Business Media. This book was released on 2008 with total page 330 pages. Available in PDF, EPUB and Kindle. Book excerpt: Step-by-step instructions that ensure successful results.

Download or read book Regulatory RNA Elements written by Philip Kensche and published by . This book was released on 2004 with total page 81 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Untranslated Gene Regions and Other Non coding Elements written by Lucy W. Barrett and published by Springer Science & Business Media. This book was released on 2013-06-26 with total page 63 pages. Available in PDF, EPUB and Kindle. Book excerpt: There is now compelling evidence that the complexity of higher organisms correlates with the relative amount of non-coding RNA rather than the number of protein-coding genes. Previously dismissed as “junk DNA”, it is the non-coding regions of the genome that are responsible for regulation, facilitating complex temporal and spatial gene expression through the combinatorial effect of numerous mechanisms and interactions working together to fine-tune gene expression. The major regions involved in regulation of a particular gene are the 5’ and 3’ untranslated regions and introns. In addition, pervasive transcription of complex genomes produces a variety of non-coding transcripts that interact with these regions and contribute to regulation. This book discusses recent insights into the regulatory roles of the untranslated gene regions and non-coding RNAs in the control of complex gene expression, as well as the implications of this in terms of organism complexity and evolution.​

Download or read book Computational Analysis of RNA binding Protein Target site Selection and Function written by Xiao Li and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Genome wide Discovery of Cis regulatory RNA Motifs and Transcriptional Regulatory Networks written by Xing Xu and published by . This book was released on 2008 with total page 420 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Molecular Biology of The Cell written by Bruce Alberts and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book A Study of Transcription Regulatory Elements in Eukaryotic Genomes with Both in Silico and Biological Methods written by Chuhu Yang and published by . This book was released on 2005 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Regulation by RNA binding Proteins written by Maria Sarah Alexis and published by . This book was released on 2019 with total page 146 pages. Available in PDF, EPUB and Kindle. Book excerpt: RNA-binding proteins (RBPs) regulate all aspects of RNA metabolism, such as splicing, localization, translation, and degradation. RNA processing is a critical component of gene expression regulation, and adaptive changes in RNA processing underlie many phenotypic differences between species. RBPs regulate RNA processing by recognizing RNA sequence elements (motifs) within RNAs. Studying the determinants of these RBP:RNA interactions is therefore key to understanding how RBPs select their targets, and how RNA processing evolves over time. This thesis presents three chapters revolving around these questions. First, I present a large-scale analysis of the evolution of gene expression across tissues, species, and studies. This study differs from previous studies in its usage of inter-sample distances to model gene expression divergence, a method that allowed us to reconcile disparate findings in the field. Second, I present a comprehensive study of the affinity landscapes of 78 human RBPs using RNA Bind-N-Seq (RBNS), an unbiased assay that determines the sequence, structure, and context preferences of RBPs. Integrated analysis of all 78 motifs reveals an unexpectedly low diversity of RNA motifs, implying frequent convergence of binding specificity towards a relatively small set of RNA motifs, many with low compositional complexity. Offsetting this trend, RBPs show extensive preferences for contextual features distinct from short linear motifs, including spaced "bipartite" motifs, biased flanking nucleotide composition, and bias away from or toward RNA structure. These results emphasize the importance of contextual features in RNA recognition, which likely enable targeting of distinct subsets of transcripts by different RBPs that recognize the same linear motif. Lastly, I compile a catalog of all known RBP specificities and examine their conservation patterns, in vivo binding patterns, and evolutionary trajectories across species. This work demonstrates that RNA regulation can be well conserved despite rapid evolution of RBP binding sites, and highlights mechanisms that may contribute to this robustness. This phenomenon is well-characterized for transcriptional regulation at promoters, but has not well been described for RNA regulation. Taken together, these studies advance our understanding of RBP target selection and how it evolves over time, thereby furthering our understanding of the basic mechanisms that govern gene regulation.

Download or read book Motif Selection Using Simulated Annealing Algorithm with Application to Identify Regulatory Elements written by Liang Chen and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Modern research on gene regulation and disorder-related pathways utilize the tools such as microarray and RNA-Seq to analyze the changes in the expression levels of large sets of genes. In silico motif discovery was performed based on the gene expression profile data, which generated a large set of candidate motifs (usually hundreds or thousands of motifs). How to pick a set of biologically meaningful motifs from the candidate motif set is a challenging biological and computational problem. As a computational problem it can be modeled as motif selection problem (MSP). Building solutions for motif selection problem will give biologists direct help in finding transcription factors (TF) that are strongly related to specific pathways and gaining insights of the relationships between genes. This study implemented an algorithm based on simulated annealing (SA) optimization algorithm for the motif selection problem, and investigated the properties of the implemented algorithm with the real world datasets (ENCODE project data).

Download or read book Computational Methods for Analyzing RNA Sequencing to Study Post Transcriptional Gene Regulation written by Ashley Anne Cass and published by . This book was released on 2018 with total page 168 pages. Available in PDF, EPUB and Kindle. Book excerpt: Since the completion of the Human Genome Project in 2003, massive DNA sequencing efforts enabled gene mapping and enhanced our understanding of genetic variation. However, exactly how the same DNA sequence in every cell of one individual leads to vast biological variation is still not fully understood. In particular, the DNA sequence does not directly contain information regarding which genes are expressed in different cell types, tissues, and disease states. With the advent of high-throughput RNA sequencing (RNA-Seq), gene expression and RNA isoform variation can be assayed cost- and time-efficiently in different conditions. In this work, we aimed to develop computational methods to analyze RNA-Seq for the purpose of elucidating mechanisms of post-transcriptional gene regulation. The first chapter briefly introduces RNA biology, including co- and post-transcriptional gene regulation concepts. The second chapter describes the identification of small cleavage-inducing RNAs and their RNA targets for degradation through bioinformatic integration of small RNA sequencing and Degradome Sequencing, the latter capturing RNA degradation products. This work revealed an expanded repertoire of small cleavage-inducing RNAs (sciRNAs) and their targets, suggesting that small RNA-mediated cleavage is more widespread than previously appreciated. Post-transcriptional regulation is often mediated by cis-regulatory elements in 5' and 3' untranslated regions (UTRs), including sciRNA target motifs. Thus, alternative transcription start sites (ATSS) and alternative polyadenylation (APA) often impact post-transcriptional gene regulation through the inclusion or exclusion of cis-regulatory elements in UTRs. In chapter three, we describe mountainClimber, a novel method that overcomes several limitations of existing approaches to identify ATSS and APA from RNA-Seq. In chapter four, we applied mountainClimber to thousands of RNA-Seq datasets derived from many human tissues in the largest study of ATSS and APA to date. In chapter five, we applied mountainClimber to chromatin-associated and poly(A)-selected RNA-Seq in murine macrophages with or without previous exposure to an endotoxin. This analysis revealed ATSS, APA, and alternative transcription end sites associated with tolerization of macrophages to endotoxins. Finally, we summarize our conclusions in chapter six.

Download or read book RNA Splicing Regulation in Drosophila Melanogaster written by Angela Norie Brooks and published by . This book was released on 2011 with total page 236 pages. Available in PDF, EPUB and Kindle. Book excerpt: A majority of metazoan genes contain introns in their primary transcripts (pre-mRNA) that require removal by the spliceosome--a cellular complex composed of protein and RNA. Upon removal of introns from the primary transcript, the remaining exonic portion of the transcript is spliced together. It is essential to remove the correct intronic portion of a primary transcript in order to produce the desired product, typically a protein-coding mRNA. Pre-mRNAs are alternatively spliced when different intron boundaries are used by the spliceosome, thus creating different mRNA products. Alternative splicing allows for an additional step of gene regulation by producing transcript isoforms that can be differentially processed in a particular tissue or developmental time point. Alternative splicing is primarily regulated by RNA binding proteins that bind to pre-mRNA and act to recruit or inhibit the spliceosome at specific splice sites. A central aim of this work is to gain a better understanding of splicing regulation by the identification and characterization of protein regulators of splicing and cis-acting splicing regulatory sequences in the model organism, Drosophila melanogaster. To identify splicing regulatory elements, many previous studies in vertebrate genomes have used computational methods. In collaboration with Anna I. Podgornaia, I applied such an approach to predict splicing regulatory elements in Drosophila melanogaster and compared them with elements found in vertebrates. I identified 330 putative splicing enhancer sequences enriched near weak 5' and 3' splice sites of constitutively spliced introns. I found that a significant proportion (58%) of D. melanogaster enhancers were previously reported as splicing enhancers in vertebrates. To provide additional evidence for the function of the intronic splicing enhancers (ISEs), I identified intronic hexamers significantly enriched within sequences phylogenetically conserved among 15 insect species. This analysis uncovered 73 putative ISEs that are also enriched in conserved regions of the D. melanogaster genome. The functions of nine enhancer sequences were verified in a heterologous splicing reporter by Julie L. Aspden, demonstrating that these sequences are sufficient to enhance splicing in vivo. Taken together, these data identify a set of predicted positive-acting splicing regulatory motifs in the Drosophila genome and highlight those regulatory sequences that are present in distant metazoan genomes. To identify and characterize splicing regulators, collaborators and I have combined RNAi and RNA-Seq to identify exons that are regulated by 58 known or putative splicing regulators. To identify and quantify alternative splicing events from RNA-Seq data, I developed the JuncBASE (Junction Based Analysis of Splicing Events) software package. For a pilot study, I identified 404 splicing events significantly affected upon depletion of pasilla. Preliminary analysis showed 879 splicing events affected by at least one of the 57 other proteins. The sequence regions upstream and within Pasilla-repressed exons and downstream of Pasilla-activated exons are enriched for YCAY repeats, which is consistent with the location of these motifs near regulated exons of the mammalian ortholog, Nova. Thus, the RNA regulatory map of Pasilla and Nova is highly conserved between insects and mammals despite the fact that the pre-mRNAs that are regulated by Pasilla and Nova are almost entirely non-overlapping. This observation strongly suggests that the regulatory codes of individual RNA binding proteins are nearly immutable, yet the regulatory modules controlled by these proteins are highly evolvable. I also present RNA regulatory maps for the four hnRNP proteins: hrp36, hrp38, hrp40, and hrp48. Lastly, I examine splicing regulation throughout the life cycle of D. melanogaster. Using transcriptome data from 30 developmental time points produced by collaborators from the modENCODE Consortium, I identified a total of 23,859 alternative splicing events in Drosophila, taking into account all transcript information from D. melanogaster annotations, short sequenced reads (Illumina RNA-Seq), sequenced cDNA, long RNA-Seq reads (454 RNA-Seq) from adult flies, and short read sequences of rRNA-depleted RNA from embryonic time points. I observed that 60.7% of intron-containing genes in D. melanogaster are alternatively spliced. Using only the Illumina RNA-Seq reads throughout development, 21,216 splicing events were expressed and 13,951 events were differentially spliced in at least one time point. I also observed exons with similar patterns of splicing changes throughout development as well as sex-biased alternative splicing. Integrating information from our pasilla study, I also observed correlations of pasilla gene expression with alternative splicing changes of its target exons throughout development.

Download or read book Scalable Genetic System Design Using Synthetic RNA Regulators written by Lei Qi and published by . This book was released on 2012 with total page 352 pages. Available in PDF, EPUB and Kindle. Book excerpt: Our ability to efficiently and predictably program cells is central to the fields of bioengineering and synthetic biology. Once thought to be a passive carrier of genetic information, RNA is now more appreciated as the main organizer of cellular networks. To harness the unique abilities of RNA molecules for programming cells, we show here how to rationally design novel synthetic RNA elements to recapitulate the functions of natural noncoding RNAs (ncRNAs), and how to assemble these synthetic elements into higher-order biological systems. To create synthetic RNA elements, we start with two primary types of ncRNA-mediated natural systems. Both modulate RNA-level regulatory signals encoded in the 5' untranslated region, and are mediated by ncRNAs. In the first system the ncRNA represses transcription elongation, whereas in the second system the ncRNA inhibits translation initiation. To create orthogonal RNA elements that work independently in the same cell, we systematically modify the RNA-RNA interaction in the natural systems. Our characterization results in families of orthogonally acting RNA elements for both transcription and translation controls. Furthermore, we develop mathematical thermodynamic models to predict new RNA elements in silico for translation controls. To engineer synthetic RNAs to sense and integrate cellular signals, we design allosteric RNA chimera molecules by fusing ncRNAs to RNA aptamers. We demonstrate the design principles for creating such chimeric RNA molecules that can sense proteins or small molecules and control transcription or translation. We show that the design strategy is modular, which allows us to reconfigure different ncRNA mutants and RNA aptamers to engineer orthogonal RNA chimeras that respond to different ligands and regulate different gene targets. We further show that multiple RNA chimeras allow logical integration of molecular signals in the same cell for cellular information processing. We assemble multiple synthetic RNA elements to create basic regulatory network motifs. These include independent control, logic control, and cascading control. We characterize the performance and properties of these engineered RNA circuits such as their time response, signal sensitivity, and noises across cell populations. We further explore a strategy that can effectively convert orthogonal translational regulators into orthogonal transcriptional regulators, which can be used to perform multi-input logic computation. In an effort to engineer feedback circuits, we demonstrate the use of translational repressor and activator based on RNA-binding proteins. The designed positive or negative feedback circuits form a basis for programming complex functions. To improve the predictability of engineered biological systems, we develop a synthetic RNA processing platform from the bacterial CRISPR genetic immune pathway. The synthetic RNA processing system can efficiently and specifically cleave desired precursor mRNAs at designed loci. Using this system, we show that transcript cleavage enables quantitative programming of gene expression by modular assembly of promoters, ribosome binding sites, cis regulatory elements, and riboregulators. These basic components can be grouped into multi-gene synthetic operons that behave predictably only after RNA processing. Physical separation of otherwise linked elements within biological assemblies allows design of sophisticated RNA-level regulatory systems that are not possible without it. Thus, our results exemplify a crucial design principle based on controllable RNA processing for improving the modularity and reliability of genetic systems. To sum, our work established bacterial ncRNAs as an intriguing engineering substrate for scalable genetic circuit design and for programming cells. We provide a set of engineering principles for designing synthetic RNA elements as well as using them to sense signals and form genetic circuits. Our RNA-based engineering platform provides a versatile and powerful strategy for designing higher-order cellular information processing and computation systems, which can be readily applied to practical applications including chemical production, environment remediation, and therapeutics.