Download or read book MicroRNA Regulation of Central Nervous System Development and Their Species specific Role in Evolution written by Hayley Sarah McLoughlin and published by . This book was released on 2013 with total page 106 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic dissection of loci important in the control of neurogenesis has improved our understanding of both the evolutionarily conserved and divergent processes in neurodevelopment. These loci include not only protein coding genes [1, 2], but also noncoding RNAs [3-5]. One important family of non-coding RNAs is miRNAs, which control gene expression fundamental in developmental regulation and mature cell maintenance [3, 5-9]. Here, we will first focus our efforts by surveying miRNA regulation in the developing brain. We hypothesize a strong regulatory role of miRNAs during proliferation, cell death, migration and differentiation in the developing mammalian forebrain that has yet to be adequately described in the literature. Second, we will assess miRNA's role in the evolutionary divergence of brain-related gene expression. We hypothesize that a human specific single nucleotide change(s) in the miRNA recognition element of transcription factors 3' untranslated regions contributes to species-specific differences in transcription factor expression and ultimately alters regulatory function.

Download or read book Regulatory RNAs in the Nervous System 2nd Edition written by Tommaso Pizzorusso and published by Frontiers Media SA. This book was released on 2018-11-13 with total page 346 pages. Available in PDF, EPUB and Kindle. Book excerpt: Until about a decade ago, the non-coding part of the genome was considered without function. RNA sequencing studies have shown, however, that a considerable part of the non-coding genome is transcribed and that these non-coding RNAs (nc-RNAs) can regulate gene expression. Almost on weekly basis, new findings reveal the regulatory role of nc-RNAs exert in many biological processes. Overall, these studies are making increasingly clear that, both in model organisms and in humans, complexity is not a function of the number of protein-coding genes, but results from the possibility of using combinations of genetic programs and controlling their spatial and temporal regulation during development, senescence and in disease by regulatory RNAs. This has generated a novel picture of gene regulatory networks where regulatory nc-RNAs represent novel layers of regulation. Particularly well-characterized is the role of microRNAs (miRNAs), small nc-RNAs, that bind to mRNAs and regulate gene expression after transcritpion. This message is particularly clear in the nervous system, where miRNAs have been involved in regulating cellular pathways controlling fundamental functions during development, synaptic plasticity and in neurodegenerative disease. It has also been shown that neuronal miRNAs are tightly regulated by electrical activity at the level of transcription, biogenesis, stability and specifically targeted to dendrites and synapses. Deregulation of expression of miRNAs is proposed not only as potential disease biomarker, but it has been implicated directly in the pathogenesis of complex neurodegenerative disease. This so-called RNA revolution also lead to the exploitation of RNA interference and the development of related tools as potential treatment of a vast array of CNS disease that could benefit from regulation of disease-associated genes. In spite of these advancements, the relatively young age of this field together with the inherent high molecular complexity of RNA regulation of biological processes have somewhat hindered its communication to the whole of the neuroscience community. This Research Topic aims at improving this aspect by putting around the same virtual table scientists covering aspects ranging from basic molecular mechanisms of regulatory RNAs in the nervous system to the analysis of the role of specific regulatory RNAs in neurobiological processes of development, plasticity and aging. Furthermore, we included papers analyzing the role of regulatory RNAs in disease models from neuromuscular to higher cognitive functions, and more technically oriented papers dealing with new methodologies to study regulatory RNA biology and its translational potential.

Download or read book Exploring the Regulatory Roles of MicroRNAs in Mammalian Development written by Grace Xinying Zheng and published by . This book was released on 2010 with total page 176 pages. Available in PDF, EPUB and Kindle. Book excerpt: microRNAs (miRNAs) are ~22-nt long short RNAs that regulate gene expression in organisms ranging from plants to animals. In mammals, miRNAs post-transcriptionally repress gene expression by primarily binding to the 3' untranslated region (3' UTR) of target mRNAs. Although hundreds of miRNAs have been discovered, targets of most miRNAs and the method by which they affect their biological function remain elusive. To better understand the role of miRNAs in fundamental cellular processes, we characterized enriched miRNA populations in three distinct murine developmental programs, T lymphocytes, embryonic stem cells, and the placenta. We started exploring the role of miRNAs in T lymphocytes by globally characterizing short RNA expression during key developmental stages of T lymphocytes. Our results showed that a distinct set of miRNAs is enriched in each stage. In particular, miR-181 is elevated at the double positive (DP) stage, when thymocytes expressing both CD4 and CD8 undergo positive and negative selection. We found that miR-181 can repress the expression of Bcl-2, CD69, and the T cell receptor, all of which are involved in positive selection. Analysis of short RNAs in T lymphocytes also revealed a novel miRNA cluster, the Sfmbt2 miRNA cluster, named as such since it maps to an intron of the Sfmbt2 gene, a Polycomb Group gene. Instead of studying this cluster in T lymphocytes, we decided to use embryonic stem (ES) cells as this cluster is also expressed in ES cells and the cells are more conducive to lab experimentation. This cluster contains several miRNA families, and we addressed the function of one miRNA family, miR-467a, as it shares target specificity with other highly abundant miRNAs in ES cells. Gain and loss of function assays showed that this family of miRNAs can promote cell survival by advancing the G1 to S phase transition. In addition, they target certain proapoptotic factors to buffer ES cells from apoptosis, especially in the context of genotoxic stress. The Sfmbt2 cluster is a mouse-specific miRNA cluster, and individual members have been uniquely amplified in the Sfmbt2 locus. We developed a method to explore the impact of species-specific miRNAs on the evolution of 3' UTRs, and found that target sites of many miRNAs show positive selection. In particular, mouse target sites have evolved to specifically gain binding sites (mouse-specific targets) for some Sfmbt2 miRNAs, several of which are enriched in the placenta. These mouse-specific targets are enriched in pathways regulating cell survival, implicating the Sfmbt2 miRNA cluster as a possible promoter to placental growth. Our studies in T lymphocytes, ES cells and the placenta have revealed important roles of miRNAs in shaping 3' UTR evolution, and mammalian development. Several novel miRNA targets we uncovered are important regulators of differentiation, cell cycle, and apoptosis. Understanding their functions will not only shed light on their roles in normal physiology, but also generate useful insights that can be applied to cancer and reprogramming.

Download or read book microRNA Regulation in Health and Disease written by Clifford J. Steer and published by MDPI. This book was released on 2020-02-21 with total page 154 pages. Available in PDF, EPUB and Kindle. Book excerpt: MicroRNAs (miRNAs) are small regulatory RNAs that play a crucial role in posttranscriptional gene regulation. Over two thousand miRNAs have been identified in humans, and many of them are conserved in other species. miRNAs are implicated in fundamental cellular functions, including development and disease. In the last decade, there has been an overwhelming amount of data contributing to the understanding of miRNA biogenesis and their target genes. Moreover, a significant amount of work has been carried out in developing miRNA biomarkers and therapeutics for various disease conditions. RNA-based markers and therapeutics have been proven to have a clinical impact, and many of these miRNA-based therapies are at various stages of human clinical trials and clinical applications. Notably, miRNAs are also found in exosomes, and are considered to impart intercellular communication and function via several different modalities, including tunneling nanotubes. In spite of our understanding of miRNA biology and function, there are many challenges in effectively using miRNAs as biomarkers and therapeutic agents in clinical applications. In this Special Issue, we are inviting reviews, perspectives, and original research articles to address some of these challenges. Topics will include, but are not limited to, miRNA biogenesis, clinical applications, extracellular function, biomarkers, miRNA immune regulation, signaling pathways, and preclinical models.

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 Microrna Functions in the Nervous System of Drosophila Melanogaster written by Kailiang Sun and published by . This book was released on 2014 with total page 450 pages. Available in PDF, EPUB and Kindle. Book excerpt: microRNAs (miRNAs) are a class of 2̃2 nucleotide small non-coding RNAs that regulate gene expression at the post-transcriptional level. Primary miRNA transcripts bear hairpins that are processed sequentially by the RNase III enzymes Drosha and Dicer into mature small RNAs that associate with Argonaute proteins. The sequence of the miRNA, particularly nucleotides 28̃ (the "seed" region), guides the Argonaute effector complex to target transcripts for degradation and/or translational repression. The limited requirement of complementarily between the miRNA and targets allows most miRNAs to regulate tens to hundreds of transcripts. Thus, almost all biological processes are subject to the control by miRNAs, although the biological consequences of this regulation often appear to be subtle. Unique characteristics of the nervous system including high diversity of neuronal subtypes and extreme morphologies of mature neurons entail the requirement for meticulous gene expression control; the particular abundance of miRNAs in the nervous system and extensive targeting of the neural transcripts suggest that miRNAs play extraordinary roles in neural development and function. This thesis examines the in vivo genetic functions of several neural miRNAs in the Drosophila system. Chapter 2 describes characterization of the mutant of Drosophila miR-124, an evolutionarily conserved miRNAs with restricted expression in the central nervous system. While miR-124 is largely dispensable for gross aspects of neuronal specification and differentiation, it fine-tunes target gene expression in neuronal lineage cells and facilitates the molecular transition of neuroblasts to neurons. Moreover, multiple components of the retrograde BMP signaling pathway is coordinately targeted by miR-124 and may mediate the miR-124 regulation of synaptic activity at the neuromuscular junction. Chapter 3 investigates the function of miR-124 in adult animals. It modulates the circadian behavior in adult flies and loss of this miRNA strongly suppresses the anticipatory activities at both morning and evening. Given the normal capability of core pacemaker neurons to drive rhythmic behavior in constant conditions, we infer that miR-124 acts in the output pathway of the circadian system. Although many miRNAs can be deleted without profound phenotypic consequences, miR-279 is among the very few miRNAs isolated from loss-of-function forward genetic screens. It was initially recognized as an essential regulator of neuronal specification, and later found to be required in multiple developmental and behavioral conditions. In Chapter 4, we conducted a thorough genetic analysis of the mir-279 locus, and unexpectedly found that the neighboring locus miR-996 contributes to all described mir-279 phenotypes. These miRNAs share the seed region but are otherwise divergent in sequence. Nonetheless, these miRNAs are able to fully replace the function of each other under physiological conditions, indicating the dominance of the miRNA seed for target recognition. I conclude this dissertation with a discussion of future directions and challenges regarding the study of these miRNAs. Taken together, these studies illustrated the basic properties of miRNA activity and demonstrated the diverse roles of miRNAs in the nervous system in both developmental and post-developmental settings.

Download or read book Addressing Functional and Evolutionary Implications of MicroRNA Variation at the DNA and RNA Levels in Primates written by Alicia Gallego Jiménez and published by . This book was released on 2018 with total page 195 pages. Available in PDF, EPUB and Kindle. Book excerpt: MicroRNAs are small non-coding RNAs with crucial roles in gene regulation and whose contribution to animal evolution has been largely demonstrated. In this thesis we explored some functional consequences of microRNA sequence variation and their possible effects in primate evolution. We first evaluated microRNA nucleotide variation at the genomic level in great apes. Taking advantage of recently published whole-genome sequencing data from 82 individuals including oragutans, gorillas, bonobos, chimpanzees and humans, we analyzed microRNA sequence conservation patterns, both among and within populations. We observed that the entire microRNA mature region was significantly conserved, suggesting its central role for the microRNA regulatory function. We additionally observed that more conserved microRNAs tend to be older, duplicated, clustered, highly associated with disease and show higher expression levels. Further functional analyses revealed that lineage-specific changes in the microRNA mature sequences and/or in the length of the precursor molecules of mir-299, mir-503, mir-508 and mir-541 altered their expression levels and redirected the spectrum of target genes and regulatory networks, some of them linked to neuronal functions. We secondly investigated microRNA sequence variation generated by RNA editing. Focusing on mir-376a1 we studied the RNA editing patterns among different primate individuals including human placenta and macaque, gorilla, chimpanzee and human brain cortex samples. Although mir-376a1 editing showed high inter-individual variation, it was more frequently detected in brain than in placenta and in one particular site. This highly edited site conferred the highest stability to the hairpin molecule, revealing the important contribution of RNA editing to the stability of the transcripts. In summary, we provide evidence on how DNA and RNA nucleotide changes may drive microRNA diversification and redefine new regulatory functions, which could have importantly contributed to primate phenotypic diversification processes and to the recent evolution of our species.

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 MicroRNAs written by Krishnarao Appasani and published by Cambridge University Press. This book was released on 2009-08-20 with total page 580 pages. Available in PDF, EPUB and Kindle. Book excerpt: MicroRNAs (miRNAs) are RNA molecules, conserved by evolution, that regulate gene expressions and their recent discovery is revolutionising both basic biomedical research and drug discovery. Expression levels of MiRNAs have been found to vary between tissues and with developmental stages and hence evaluation of the global expression of miRNAs potentially provides opportunities to identify regulatory points for many different biological processes. This wide-ranging reference work, written by leading experts from both academia and industry, will be an invaluable resource for all those wishing to use miRNA techniques in their own research, from graduate students, post-docs and researchers in academia to those working in R&D in biotechnology and pharmaceutical companies who need to understand this emerging technology. From the discovery of miRNAs and their functions to their detection and role in disease biology, this volume uniquely integrates the basic science with industry application towards drug validation, diagnostic and therapeutic development. Forewords by: Sidney Altman, Yale University, Winner of the Nobel Prize in Chemistry, 1989 and Victor R. Ambros, Dartmouth Medical School, Co-discoverer of MicroRNAs

Download or read book Functional Micro Ribonucleic Acid Landscape of Mammalian Development written by Arvind Ravi and published by . This book was released on 2011 with total page 245 pages. Available in PDF, EPUB and Kindle. Book excerpt: MicroRNAs (miRNAs) constitute a class of ~22 nucleotide RNAs with broad regulatory roles in gene expression. Dependent largely on the enzyme Dicer for their generation from longer precursor transcripts, mammalian miRNAs direct posttranscriptional repression of mRNAs based on complementarity to sites in their 3' UTRs. To better understand how these regulators impact fundamental processes such as development and cancer, we explored the functional consequences of Dicer loss and subsequent miRNA loss across a range of embryonic and somatic tissues. In embryonic stem (ES) cells, we identified a latent susceptibility to genotoxic stress following deletion of Dicer. Re-expression of the abundant miR-290-295 cluster or knockdown of two novel targets, Caspase 2 and Ei24, could partially restore cell survival after DNA damage, implicating them as important players in a larger stress-responsive ES network under miRNA control. To better understand changes in miRNA and target repertoires at a global scale, we applied a novel evolutionary analysis to the mouse genome designed to speciesspecific innovations. Using this method, we uncovered the genome-wide signature of miRNAs functionally related to the miR-290-295 cluster that we term the Sfmbt2 cluster. In addition to ES cells, placental tissues express these miRNAs at high levels suggesting that mice have co-opted an existing proliferative network to support rapid placental growth. Finally, we evaluated Dicer loss in two transformed somatic cell types, namely sarcoma cells and mesenchymal stem cells. Surprisingly, these cells tolerated Dicer deletion without loss of viability and retained several properties of their Dicer intact counterparts including surface marker expression and tumorigenicity. Comparison of expression data in these cells and ES cells revealed that while many miRNA targets show relatively little change before and after Dicer loss, a subset of genes that differ between embryonic and somatic cells may be controlled in large part by cell type specific miRNAs. In summary, these data shed light on many fundamental aspects of miRNA function in mammalian cells, expanding our understanding of molecular targets as well their downstream cellular roles. As our knowledge about short RNA regulation grows, we are sure to continue uncovering important connections between post-transcriptional regulation and the underlying biology of human development and disease.

Download or read book The Role of MicroRNA mediated Gene Regulation in Development written by Russell Posner and published by . This book was released on 2021 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: In the face of random perturbations in environment as well as genetic mutations, complex organisms manage to maintain remarkably robust developmental stability. Despite originating from a single cell and sharing a common genome, tissue-based organisms contain many different cellular phenotypes. The robustness of the developmental programs of these organisms depends on their underlying gene regulatory network (GRN), which is composed of a diverse set of mechanisms that help the cell achieve a desired state and stay there. One curiosity of tissue-based organisms is their near-universal dependence on non-coding RNAs, of which the largest class is the 18-22nt long microRNAs (miRNAs). These short RNAs typically, but not always, repress the translation of messenger RNAs (mRNAs) into functional proteins in a sequence-specific manner. Nonetheless, identifying the relationship between tissue-based organism development and miRNAs has been challenging. Within a single model organism, a large number of synthesis and functional pathways contribute to this overall effect. Furthermore, despite their overall dependence on miRNAs, it has been demonstrated that only a small subset of the total set of DNA-encoded miRNAs (the miRNAome) is required for proper development, and the loss of individual miRNAs often causes no change in phenotype. This dissertation aims to postulate a "fundamental law of miRNAs" in the development of these organisms. The complexities of miRNA-mediated gene regulation can often obscure their commonalities; by using a common abstraction of GRNs and gene expression, my aim is to show that miRNA-mediated regulation is innately tied to the notion of stem cells and cell differentiation. Using a multiple different models of gene expression and cell differentiation, I show how the specific type of regulation imparted by miRNAs can help create a stable, undifferentiated state and control the duration of that state. This role for miRNAs is supported independently by each model and agrees with experimentally-observed data.

Download or read book Evolution of Neurosensory Cells and Systems written by Bernd Fritzsch and published by CRC Press. This book was released on 2022-05-08 with total page 338 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is an overview of primary sensory maps of vertebrates, characterized by continuous and discrete properties. The eight primary sensory maps of vertebrates have unique features and use distinct molecular cues, cell cycle exit, and activity combinations during development, regeneration, and plasticity. As an introduction and overview, the book provides a short overview for all eight sensory senses and presents through evolution and gene regulatory networks, the molecular cues needed for sensory processing. Independent contributions are included for olfactory, vision, trigeminal, taste, vestibular, auditory, lateral line, and electroreception.

Download or read book MicroRNA Control of Neural Progenitor Maintenance and Specification written by Laura Ioana Hudish and published by . This book was released on 2016 with total page 142 pages. Available in PDF, EPUB and Kindle. Book excerpt: During neural development, progenitors both divide to expand the neural progenitor (NP) population and differentiate as neurons and glia. This balance of proliferation and differentiation is crucial to the proper development of the central nervous system (CNS). This balance appears to be regulated by multiple different mechanisms including apico-basal polarization by Partitioning defective proteins (Par) as well as Hedgehog signaling, which in addition to its role in dorso-ventral patterning also promotes progenitor proliferation. How both of these pathways are modulated at the end of neurogenesis remains poorly understood. Using bioinformatics we identified the polarity genes pard3 and prkci as candidate targets for microRNA-219 (miR-219). miR-219-deficient zebrafish embryos have a deficit of oligodendrocytes, the myelinating glial cells of the CNS. Because a disruption in polarity could affect the types of cell divisions that NPs undergo, thus altering the balance of cell types that arise, we hypothesized that neural precursor maintenance is regulated by modulation of polarity cues through miR-219. We found that miR-219 inhibited expression of pard3 and prkci mRNAs via target sites in the 3’ untranslated region. These data support the role of miR-219 in downregulating expression of Par polarity proteins at the end of neurogenesis. In addition, we also found that Sonic Hedgehog (Shh) signaling was significantly increased in miR-219 morphants, suggesting a role for miR-219 in regulating the levels of Shh. Using prkci mutant zebrafish embryos we found that reduction of apical Par proteins results in a reduction of Shh signaling. These data provide evidence for a new mechanism of NP regulation, in which miR-219 downregulates apical Par proteins and Shh at the end of neurogenesis.

Download or read book microRNAs in Development written by and published by Academic Press. This book was released on 2012-11-15 with total page 327 pages. Available in PDF, EPUB and Kindle. Book excerpt: This new volume in the Current topics in Developmental Biology series concentrates on MicroRNAs in Development. It includes chapters on such topics as miRNA networks in neuronal development, let-7 in development, and Hox networks and miRNA. With an international team of authors, this volume is a must-have addition for researchers and students alike. Concentrates on microRNAs in development Includes chapters on such topics as miRNA networks in neuronal development, let-7 in development, and Hox networks and miRNA With an international team of authors, this volume is a must-have addition for researchers and students alike

Download or read book Regeneration and Brain Repair written by Daniella Rylander Ottosson and published by Frontiers Media SA. This book was released on 2021-07-15 with total page 140 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book The RNA Revolution in Embryonic Development and Cell Differentiation in Health and Disease written by Francesco Fazi and published by Frontiers Media SA. This book was released on 2021-11-02 with total page 229 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Polyploidy and Genome Evolution written by Pamela S. Soltis and published by Springer Science & Business Media. This book was released on 2012-10-03 with total page 417 pages. Available in PDF, EPUB and Kindle. Book excerpt: Polyploidy – whole-genome duplication (WGD) – is a fundamental driver of biodiversity with significant consequences for genome structure, organization, and evolution. Once considered a speciation process common only in plants, polyploidy is now recognized to have played a major role in the structure, gene content, and evolution of most eukaryotic genomes. In fact, the diversity of eukaryotes seems closely tied to multiple WGDs. Polyploidy generates new genomic interactions – initially resulting in “genomic and transcriptomic shock” – that must be resolved in a new polyploid lineage. This process essentially acts as a “reset” button, resulting in genomic changes that may ultimately promote adaptive speciation. This book brings together for the first time the conceptual and theoretical underpinnings of polyploid genome evolution with syntheses of the patterns and processes of genome evolution in diverse polyploid groups. Because polyploidy is most common and best studied in plants, the book emphasizes plant models, but recent studies of vertebrates and fungi are providing fresh perspectives on factors that allow polyploid speciation and shape polyploid genomes. The emerging paradigm is that polyploidy – through alterations in genome structure and gene regulation – generates genetic and phenotypic novelty that manifests itself at the chromosomal, physiological, and organismal levels, with long-term ecological and evolutionary consequences.