Download or read book MicroRNA Regulatory Network Structure and Function written by Zengrong Liu and published by Springer. This book was released on 2018-11-02 with total page 231 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book discusses topics related to the topological structure and biological function of gene networks regulated by microRNAs. It focuses on analyzing the relation between topological structure and biological function, applying these theoretical results to gene networks involving microRNA, illustrating their biological mechanisms, and identifying the roles of microRNA in controlling various phenomena emerging from the networks. In addition, the book explains how to control the complex biological phenomena using mathematical tools and offers a new perspective on studying microRNA. It is a useful resource for graduate students and researchers who are working on or interested in microRNAs and gene network.
Download or read book Divide and Conquer written by Ravi Krishnakant Patel and published by . This book was released on 2020 with total page 245 pages. Available in PDF, EPUB and Kindle. Book excerpt: Post-transcriptional regulation of gene expression is essential for cell function. MicroRNAs (miRNAs), small (~22nt) non-coding RNAs, are negative regulators of post-transcriptional expression. MiRNAs recruit the RNA induced silencing complex (RISC), which includes an Argonaute (AGO) protein, to partially complementary target sites located in 3' untranslated regions (UTRs), and induce accelerated mRNA decay and translational inhibition of target mRNAs. Each miRNA has potential to regulate many hundreds of mRNAs via this pathway. Although, miRNAs typically elicit a modest effect per mRNA, hundreds of such small changes result in a substantial cumulative impact on the transcriptome. Additionally, miRNA regulatory networks incorporate master regulators such as transcription factors downstream of miRNAs, enabling miRNAs to trigger substantial changes in gene regulatory networks. Understanding the biological impact of miRNAs requires knowledge of their targets, and robust distinction of miRNA direct targets from cascading downstream regulatory changes remains challenging. In this work, I developed a simple experimental approach to robustly uncouple post-transcriptional and transcriptional changes using RNA-seq and Precision Run-On sequencing (PRO-seq), a method for profiling actively transcribing RNA polymerases. The net change in mRNA abundance results from changes in synthesis and decay. I demonstrated that by subtracting the changes in mRNA synthesis (PRO-seq) from the changes in mRNA abundance (RNA-seq), a robust estimate of post-transcriptional regulation by miRNAs could be derived. I refer to this approach as CARP: Combined Analysis of RNA-seq and PRO-seq. Using CARP, I successfully separated true direct targets of specific miRNAs from the downstream indirect changes, which I validated using orthogonal assays such as Argonaute eCLIP-seq and ribosome profiling. Additionally, CARP analysis revealed that the majority of miRNAs used in the study elicited sizable indirect targeting at both transcriptional and post-transcriptional levels, which are often disregarded. Using motif enrichment analysis, I found candidate transcription factors underlying the miRNA-mediated indirect regulation at transcriptional level. I also demonstrated that CARP facilitates effective dissection of complex regulatory changes triggered by miRNAs. Furthermore, my analysis revealed that many miRNAs elicit discernible repression of target sites located in open reading frames (ORFs); the significance of ORF target sites is a potentially important aspect of miRNA biology, but the extent to which it occurs has been controversial. My data demonstrated that while ORF sites to certain miRNAs often mediate subtle repression, their likely role is in assisting the miRNA-mediated regulation of weaker 3'UTR sites to collectively elicit significant post-transcriptional repression of the target mRNA. Overall, the tools I developed in my graduate work facilitate robust distinction of direct target from indirect regulatory changes aiding in the study of miRNA regulatory networks at the systems-level. Finally, I apply CARP and other genomic approaches to better understand biological roles of miRNAs in the immune response of CD8+ T-cells in mouse models.
Download or read book An investigation of microRNA target regulation mechanisms using an integrative approach written by Ulf Schmitz and published by Logos Verlag Berlin GmbH. This book was released on 2015-06-29 with total page 204 pages. Available in PDF, EPUB and Kindle. Book excerpt: This work is a showcase for the integration of systems biology and bioinformatics tools, algorithms and models for deciphering biological phenomena. More specifically, it integrates (i) prediction algorithms for identifying and characterizing molecular interactions, (ii) structural modelling of molecule complexes, (iii) network analysis approaches, and (iv) mathematical modelling and simulation. Two comprehensive workflows are implemented for the analysis of collective target gene regulation by microRNAs and for the prediction of cooperating microRNA pairs and their mutual target genes. In two case studies mechanisms of fine-tuned target gene regulation are revealed for different cellular processes and the phenomenon of cooperative target regulation is identified as frequent mechanism of gene regulation in humans.
Download or read book MicroRNA Cancer Regulation written by Ulf Schmitz and published by Springer Science & Business Media. This book was released on 2013-02-03 with total page 352 pages. Available in PDF, EPUB and Kindle. Book excerpt: This edited reflects the current state of knowledge about the role of microRNAs in the formation and progression of solid tumours. The main focus lies on computational methods and applications, together with cutting edge experimental techniques that are used to approach all aspects of microRNA regulation in cancer. We are sure that the emergence of high-throughput quantitative techniques will make this integrative approach absolutely necessary in the near future. This book will be a resource for researchers starting out with cancer microRNA research, but is also intended for the experienced researcher who wants to incorporate concepts and tools from systems biology and bioinformatics into his work. Bioinformaticians and modellers are provided with a general perspective on microRNA biology in cancer, and the state-of-the-art in computational microRNA biology.
Download or read book MicroRNAs in Cancer written by Cesar Lopez-Camarillo and published by CRC Press. This book was released on 2013-02-22 with total page 426 pages. Available in PDF, EPUB and Kindle. Book excerpt: MicroRNA (miRNA) biology is a cutting-edge topic in basic as well as biomedical research. This is a specialized book focusing on the current understanding of the role of miRNAs in the development, progression, invasion, and metastasis of diverse types of cancer. It also reviews their potential for applications in cancer diagnosis, prognosis, and th
Download or read book Roles and regulatory mechanisms of microRNA in plant development evolution and adaptation written by Lei Li and published by Frontiers Media SA. This book was released on 2022-09-23 with total page 152 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Computational Methods of Inferring Context specific MicroRNA Regulatory Networks written by Yue Li and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book RNA Infrastructure and Networks written by Lesley J. Collins and published by Springer Science & Business Media. This book was released on 2011-09-15 with total page 297 pages. Available in PDF, EPUB and Kindle. Book excerpt: RNAs form complexes with proteins and other RNAs. The RNA‐infrastructure represents the spatiotemporal interaction of these proteins and RNAs in a cell‐wide network. RNA Infrastructure and Networks brings together these ideas to illustrate the scope of RNA‐based biology, and how connecting RNA mechanisms is a powerful tool to investigate regulatory pathways. This book is but a taste of the wide range of RNA‐based mechanisms that connect in the RNA infrastructure.
Download or read book Plant MicroRNAs written by Stefan de Folter and published by Humana Press. This book was released on 2019-01-31 with total page 363 pages. Available in PDF, EPUB and Kindle. Book excerpt: This detailed volume provides a collection of protocols for the study of miRNA functions in plants. Beginning with coverage of miRNA function, biogenesis, activity, and evolution in plants, the book continues by guiding readers through methods on the identification and detection of plant miRNAs, bioinformatic analyses, and strategies for functional analyses of miRNAs. 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. Authoritative and cutting-edge, Plant MicroRNAs: Method and Protocols aims to ensure successful results in the further study of this vital area of plant science.
Download or read book Hormones Metabolism and the Benefits of Exercise written by Bruce Spiegelman and published by Springer. This book was released on 2018-03-07 with total page 108 pages. Available in PDF, EPUB and Kindle. Book excerpt: The world is faced with an epidemic of metabolic diseases such as obesity and type 2 diabetes. This is due to changes in dietary habits and the decrease in physical activity. Exercise is usually part of the prescription, the first line of defense, to prevent or treat metabolic disorders. However, we are still learning how and why exercise provides metabolic benefits in human health. This open access volume focuses on the cellular and molecular pathways that link exercise, muscle biology, hormones and metabolism. This will include novel “myokines” that might act as new therapeutic agents in the future.
Download or read book Developmental Timing written by and published by Academic Press. This book was released on 2013-09-04 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This new volume of Current Topics in Developmental Biology covers developmental timing, with contributions from an international board of authors. The chapters provide a comprehensive set of reviews covering such topics as the timing of developmental programs in Drosophila, temporal patterning of neural progenitors, and environmental modulation of developmental timing.
Download or read book Role of Transcription Factor microRNA Feedback Circuits in the Canalization of Human Regulatory Networks written by Daniel R. Chee and published by . This book was released on 2019 with total page 64 pages. Available in PDF, EPUB and Kindle. Book excerpt: Complex interactions between hundreds of transcription factors underlie the gene expression profiles that give rise to cellular form and function. However, it is still not entirely understood how organisms faithfully recapitulate complex phenotypes through differentiation and development. Here I discuss the role MicroRNAs play in the robustness of human gene regulatory networks. Specifically, I find that TF-miRNA negative feedback circuits are significantly enriched in networks across 156 diverse cell types and that the motifs occur preferentially with highly connected TFs that drive local network architecture. My work also implicates TF-miRNA circuits in the reinforcement of cell fate decisions, and expression changes observed during differentiation. Further to the aforementioned, a second aspect of my work has focused on approaches for targeted manipulation and perturbation of regulatory elements and networks. Although genome editing has now become commonplace, tools and approaches for precisely manipulating gene expression and regulatory networks are still lacking. Here I describe development of novel computational tools for the efficient design and synthesis of potent and specific Transcriptional Activator-Like Effectors (TALEs) and TALE nucleases (TALENs).
Download or read book Gene Network Inference written by Alberto Fuente and published by Springer Science & Business Media. This book was released on 2014-01-03 with total page 135 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents recent methods for Systems Genetics (SG) data analysis, applying them to a suite of simulated SG benchmark datasets. Each of the chapter authors received the same datasets to evaluate the performance of their method to better understand which algorithms are most useful for obtaining reliable models from SG datasets. The knowledge gained from this benchmarking study will ultimately allow these algorithms to be used with confidence for SG studies e.g. of complex human diseases or food crop improvement. The book is primarily intended for researchers with a background in the life sciences, not for computer scientists or statisticians.
Download or read book Handbook of Computational Molecular Biology written by Srinivas Aluru and published by CRC Press. This book was released on 2005-12-21 with total page 1108 pages. Available in PDF, EPUB and Kindle. Book excerpt: The enormous complexity of biological systems at the molecular level must be answered with powerful computational methods. Computational biology is a young field, but has seen rapid growth and advancement over the past few decades. Surveying the progress made in this multidisciplinary field, the Handbook of Computational Molecular Biology of
Download or read book Understanding MicroRNA Biogenesis and Function Through Annotation of Primary MiRNA Transcripts and Characterization of Functional Interactions Between MicroRNAs and RNA binding Proteins written by Dustin Haskell and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The gene expression programs that establish and maintain cellular and organism homeostasis require precise, potent, and multifaceted forms of regulation. Post-transcriptional mechanisms of regulation rely on the combinatorial action of two major classes of effectors: RNA-binding proteins (RBPs) and microRNAs (miRNAs). miRNAs are small noncoding RNAs that interact with many developmental and cellular pathways by repressing gene targets and are therefore critical to the execution of gene expression programs. miRNA dysfunction can lead to widespread disruption of gene regulatory networks, contributing to the occurrence and progression of developmental disorders and pathologies such as cancer. Most miRNAs are generated through a complex biogenesis that includes RNA Pol II-dependent transcription, successive enzymatic processing by endonucleases DRSH-1 and DCR-1 and loading into Argonaute proteins to form the miRNA induced silencing complex (miRISC). Guided by the loaded miRNA, miRISC binds the 3'UTR of a target mRNA and actively downregulates its expression through translation repression or mRNA degradation. Mature miRNAs are produced through a series of enzymatic processing steps. Initial processing of primary miRNA gene transcripts (pri-miRNAs), performed by endonuclease DRSH-1, often occurs co-transcriptionally or shortly thereafter. Hence, pri-miRNA transcripts are largely absent from traditional RNA sequencing data sets, and thus difficult to characterize. The lack of primary miRNA annotations has hindered efforts to understand the mechanisms that modulate miRNA gene expression and complicated our ability to study the regulation of pri-miRNA processing. To fill this gap, we used an auxin-induced degron system to conditionally deplete DRSH-1 and greatly reduce processing of pri-miRNAs, leading to their accumulation. Subsequent RNAseq experiments identified pri-miRNAs and allowed for their annotation, revealing previously unappreciated, complex genomic features of the miRNA loci and providing an essential resource for future studies of miRNA regulation. In addition, we identified>300 novel transcripts, uncovering existence of previously uncharacterized RNAs that may depend on DRSH-1 for processing, thus expanding the known C. elegans transcriptome. Once miRNAs are processed to their mature form, they exert their repressive functions by targeting miRISC to the 3' UTRs of mRNA transcripts through partial base-pair complementarity. RBPs represent an important class of molecules that contribute to post-transcriptional regulation of gene expression, however, the extent of functional RBP coordination with miRNAs is largely unexplored. Similarly, a comprehensive understanding of how RBPs coordinate with miRNAs to regulate gene expression is lacking. To address the potential functional interaction between miRNAs and RBPs, I performed a targeted RNAi screen of 27 K-homology (KH) domain RBPs to identify factors that genetically interact with five miRNA sensitized mutant backgrounds. I identified multiple KH domain RBPs that functionally interact with all or some of miRNAs families tested, expanding our understanding of the crosstalk between two classes of post-transcriptional gene regulators. Overall, this work has expanded our understanding of miRNA gene structure and the characteristics of primary miRNA transcripts, ultimately providing a valuable tool for future study of pri-miRNA transcription and processing. Furthermore, this work established a functional relationship between several RNA-binding proteins and developmental miRNA pathways, thus identifying candidates for future studies of functional RBP-miRNA interactions.
Download or read book Role of the MicroRNA MiR 124 in the Regulatory Network Governing PNS Development in Ciona Intestinalis written by and published by . This book was released on 2013 with total page 211 pages. Available in PDF, EPUB and Kindle. Book excerpt: MicroRNAs are fundamental regulators of gene expression whose dysfunction has been linked to many cancers and other diseases. Although many individual microRNA-gene interactions have been studied, to fully understand the function of a microRNA we must uncover its underlying genetic regulatory networks, beginning with its upstream and downstream factors. For my thesis work I focused on the developing peripheral nervous system (PNS) of the ascidian Ciona intestinalis, and in particular the upstream and downstream factors regulating the microRNA miR-124, which I showed is expressed in the ascidian PNS and promotes sensory neuron formation. Through computational and experimental analysis of the canonical targets of miR-124, I found that miR-124 promotes neurogenesis by a feedback interaction with genes of the Notch signaling pathway. Using transgenic assays along with in situ hybridization I then demonstrated that miR-124 is activated downstream of a linear network of conserved proneural genes, which in turn are also regulated by Notch signaling. I then developed a mathematical model that explains the patterning of sensory neurons in the ascidian PNS. Using this model I showed that the regulatory network comprising miR-124, proneural genes and Notch signaling is sufficient for neuronal patterning in Ciona. Importantly, I demonstrated that miR-124 regulation of Notch signaling can be accurately incorporated into the Notch decay rate parameter of the model. Altogether, I have uncovered the core regulatory network by which miR-124 promotes neuron formation in the Ciona PNS, which should motivate future studies on this important microRNA in other animals.
Download or read book Computational Biomedicine written by Peter Coveney and published by Oxford University Press, USA. This book was released on 2014-06 with total page 294 pages. Available in PDF, EPUB and Kindle. Book excerpt: Computational Biomedicine unifies the different strands of a broad-ranging subject to demonstrate the power of a tool that has the potential to revolutionise our understanding of the human body, and the therapeutic strategies available to maintain and protect it.
