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Functional and Evolutionary Genomics of Ancient Small RNAs

古代小 RNA 的功能和进化基因组学

基本信息

批准号：
8212305
负责人：
Michael J Axtell
金额：
$ 21.99万
依托单位：
PENNSYLVANIA STATE UNIVERSITY, THE
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-02-01 至 2014-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8212305
关键词：
Address Angiosperms Animal Model Animals Applied Research Awareness Basic Science Binding Biogenesis Biological Assay Biological Models Biological Process Biomedical Research Cells Clinical Research Comparative Study DNA DNA Binding DNA-Binding Proteins Development Developmental Process Disease Embryonic Development Epitopes Evolution Gene Expression Gene Expression Regulation Gene Targeting Genes Genetic Genomics Health Hereditary Disease Human Individual Knowledge Language Life Malignant Neoplasms Mediating Methodology MicroRNAs Molecular Molecular Genetics Morphology Mosses Mouse-ear Cress Mutagenesis Mutation Organism Organogenesis Pathway interactions Pattern Phenotype Physcomitrella Planet Earth Plant Model Plants Play Polymerase Gene Process RNA Interference RNA-Directed RNA Polymerase Regulation Regulator Genes Research Resistance Role Small RNA Stimulus Study models System Techniques Testing Therapeutic Time Tissues Translating Work base biological adaptation to stress chromatin immunoprecipitation gene function genetic analysis human DICER1 protein knowledge base loss of function loss of function mutation novel overexpression plant growth/development promoter research study response tool transcription factor

项目摘要

DESCRIPTION (provided by applicant): Information encoded within linear segments of DNA (genes) is the basis for all life on planet Earth. Genes are not "on" all of the time - on the contrary, the activities of individual genes are finely tuned in response to various internal and external stimuli. Regulation of gene expression is critical for almost every biological process in humans and all other organisms. Small regulatory RNAs termed microRNAs have recently been discovered to be major components of gene expression control in both animals and plants. The regulation of specific "target" genes by microRNAs is critical for embryonic development, organogenesis, and stress responses. A core set of plant microRNAs regulate homologous targets in very different plant species; these ancient microRNA-target interactions are thought to regulate developmental processes. How do the same microRNA-target interactions guide the very different developmental patterns and morphologies of highly divergent plants? Do they ultimately control ancient, conserved suites of gene expression, or have they been differentially utilized in different lineages? This project seeks to answer these questions by using molecular genetics to elucidate the functions and regulatory networks of ancient miRNAs in two very different land plants. Specifically, this project will 1) genetically dissect the functions of the microRNA machinery in the moss P. patens, 2) analyze the functions of homologous, ancient microRNA-target interactions in two very different model plant species, P. patens and the flowering plant Arabidopsis thaliana, and 3) empirically determine and compare the gene regulatory networks controlled by ancient microRNA-target interactions in these two species. This project also will implement a novel methodology for the study of microRNA functions with the potential for broad applicability in basic and applied research. A detailed molecular picture of the evolution of critical gene regulatory networks will emerge from this work. Importantly, the core mechanisms of microRNA function are conserved between plants, animals, and humans. Indeed, the basic knowledge gained from past research on microRNAs and other small RNAs in easily studied plants has directly contributed to advances in human health research, including the use of RNA-interference to rapidly assay gene function in human cells, the growing appreciation of the roles microRNAs play in various common diseases, and the development of small RNA-based therapies for specific ailments. Further advances in the basic understanding of microRNA-controlled gene regulatory networks, derived by exploiting the powerful molecular genetic tools uniquely available in plant systems, will certainly continue to inform a wide variety of biomedical research. PUBLIC HEALTH RELEVANCE: Project Narrative Many genes have recently been shown to be controlled by microRNAs, including several implicated in cancer and other diseases, but the molecular details of microRNA functions are still largely unknown. Fundamental aspects of microRNA function appear identical in humans, animals, and plants, which allows analyses in easily manipulated organisms to inform human processes. This project will reveal basic mechanisms of microRNA-mediated gene control by defining the roles of ancient microRNAs in readily studied model organisms.

描述（由申请人提供）：编码在DNA（基因）线性片段内的信息是地球上所有生命的基础。基因并不是一直都“开启”的--相反，个体基因的活动是根据各种内部和外部刺激进行微调的。基因表达的调控对人类和所有其他生物体的几乎所有生物过程都至关重要。最近发现，称为microRNA的小调控RNA是动物和植物基因表达控制的主要成分。microRNA对特定“靶”基因的调控对于胚胎发育、器官发生和应激反应至关重要。一组核心的植物microRNA调节非常不同的植物物种中的同源靶标;这些古老的microRNA-靶标相互作用被认为调节发育过程。相同的microRNA-靶标相互作用如何指导高度分化的植物的非常不同的发育模式和形态？它们是否最终控制着古老的、保守的基因表达，或者它们是否在不同的谱系中被不同地利用？该项目试图通过使用分子遗传学来阐明两种非常不同的陆地植物中古老miRNAs的功能和调控网络来回答这些问题。具体来说，该项目将1）从遗传学上剖析苔藓P. patens中microRNA机制的功能，2）分析两种非常不同的模式植物物种P. patens和开花植物拟南芥中同源，古老的microRNA-靶标相互作用的功能，3）经验性地确定和比较这两个物种中由古老的microRNA-靶标相互作用控制的基因调控网络。该项目还将实施一种新的方法，用于研究microRNA功能，具有在基础和应用研究中广泛适用的潜力。一个详细的关键基因调控网络的进化分子图片将出现从这项工作。重要的是，microRNA功能的核心机制在植物、动物和人类之间是保守的。事实上，从过去对容易研究的植物中的microRNA和其他小RNA的研究中获得的基本知识直接促进了人类健康研究的进步，包括使用RNA干扰快速测定人类细胞中的基因功能，越来越多的人认识到microRNA在各种常见疾病中的作用，以及针对特定疾病的基于小RNA的疗法的发展。通过利用植物系统中独特的强大分子遗传工具，对microRNA控制的基因调控网络的基本理解取得了进一步的进展，肯定会继续为各种生物医学研究提供信息。公共卫生相关性：许多基因最近被证明是由microRNA控制的，包括一些与癌症和其他疾病有关的基因，但microRNA功能的分子细节在很大程度上仍然未知。microRNA功能的基本方面在人类、动物和植物中似乎是相同的，这使得在容易操纵的生物体中进行分析可以为人类过程提供信息。该项目将通过定义古老microRNA在已研究的模式生物中的作用，揭示microRNA介导的基因控制的基本机制。