Mechanisms of microRNA turnover in Arabidopsis

拟南芥中 microRNA 周转的机制

• 批准号: 8838615
• 负责人: Xuemei Chen
• 金额: $ 28.52万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8838615
• 关键词: Animal Model; Animals; Arabidopsis; Area; Biochemical; Biogenesis; Biological Process; Biology; Cell Maintenance; Cues; Defect; Development; Disease; Enzymes; Eukaryota; Exonuclease; Family; Foundations; Funding; Gene Expression; Genetic; Genomics; Goals; Grant; Hand; Human; Individual; Knowledge; Laboratories; Lead; Link; Mediating; Messenger RNA; MicroRNAs; Modeling; Molecular; Organism; Personal Satisfaction; Phosphodiesterase I; Plant Model; Plants; Positioning Attribute; Process; Regulator Genes; Research; Resources; Role; Small Interfering RNA; Small RNA; Specificity; Stem Cell Development; Stem cells; Tail; Testing; Therapeutic Agents; Transferase; United States National Institutes of Health; Vision; Work; cost; epigenetic memory; in vivo; plant growth/development; public health relevance; response

 DESCRIPTION (provided by applicant): microRNAs (miRNAs) are sequence-specific regulators of gene expression that impact almost all biological processes in diverse eukaryotes. Defects in miRNA levels or activities are associated with numerous diseases. Both biogenesis and degradation contribute to the steady-state levels of miRNAs in vivo. The basic molecular framework underlying miRNA biogenesis has been elucidated. In contrast, although studies in ciliate, algal, plant, and animal models have implicated the existence of conserved processes that degrade miRNAs and related small RNAs, such as small interfering RNAs (siRNAs) and piwi-interacting RNAs (piRNAs), the enzymes that degrade small RNAs have yet to be identified in most organisms. As such, a basic framework of miRNA degradation awaits further studies. The goal of this project is to establish such a framework. The project capitalizes on recent advances in the area of miRNA degradation made in the PI's laboratory using the Arabidopsis model. The PI's lab identified the enzymes responsible for two conserved miRNA degradation processes in eukaryotes, 3' truncation and 3' uridylation (addition of a short, U-rich tail to miRNAs). The proposed research employs a combination of genetics, genomics, and biochemical approaches to examine the activities, interdependence and concerted actions of these enzymes with the goal of establishing a general framework of miRNA degradation. The PI's lab has also gathered preliminary evidence that implicates endogenous target mimic RNAs in miRNA turnover. The project will examine how the interplay between target mimic RNAs and the general miRNA degradation machinery results in the turnover of specific miRNAs. By elucidating principles governing miRNA degradation, the project will generate far-reaching impacts. As mounting evidence points to conserved molecular mechanisms underlying miRNA degradation in diverse eukaryotes, the proposed studies using the Arabidopsis model, from which two conserved miRNA degradation processes were first described and the enzymes responsible for these processes were first identified, will establish a general framework of miRNA degradation that is likely applicable to other eukaryotes including humans. The knowledge will enrich our understanding of various biological processes that are influenced by miRNAs and enhance our ability to control miRNA abundance to treat diseases. The molecular framework of miRNA degradation is also likely applicable to siRNAs or piRNAs, which are emerging as agents that confer epigenetic memory in plants and animals, thus further broadening the impacts of the work.

 描述（由适用提供）：microRNA（miRNA）是基因表达的序列特异性调节剂，它影响了潜水员真核生物中几乎所有生物过程。 miRNA水平或活动中的缺陷与许多疾病有关。生物发生和降解都有助于体内miRNA的稳态水平。已经阐明了miRNA生物发生的基本分子框架。相反，尽管在纤毛，藻类，植物和动物模型中进行了研究，但已经实施了降解miRNA和相关的小RNA的保守过程，例如小型干扰RNA（siRNAS）和PIWI相互作用的RNA（PIRNA）（PIRNA）（PIRNA）（PIRNA），即降级小RNA的酶已被降低可识别为已被识别为众所周知的小组。因此，miRNA降解的基本框架正在等待进一步的研究。该项目的目的是建立这样的框架。该项目利用了使用拟南芥模型在PI实验室中获得的miRNA降解领域的最新进展。 PI的实验室确定了负责真核生物中两个保守的miRNA降解过程的酶，3'截断和3'尿苷（在miRNA中添加了短而富含U的尾巴）。拟议的研究员工是研究这些酶的活动，相互依存和协同行动的遗传学，基因组学和生化方法的结合，目的是建立miRNA降解的一般框架。 PI的实验室还收集了初步证据，这些证据表明在miRNA周转率中实现内源性靶标RNA。该项目将研究目标模拟RNA与一般miRNA降解机制之间的相互作用如何导致特定miRNA的营业额。通过阐明管理miRNA退化的原则，该项目将产生深远的影响。正如越来越多的证据指出，使用拟南芥模型的拟议的研究首先描述了两个保守的miRNA降解过程，首先描述了拟南芥模型的拟议研究，首先鉴定出了两个保守的miRNA降解过程，首先鉴定出了两个保守的miRNA降解过程，将首先鉴定出米尔纳降解的一般框架可能适用于其他eukaryos，首先是对这些过程的一般框架。知识将丰富我们对受miRNA影响的各种生物过程的理解，并增强我们控制miRNA丰度治疗疾病的能力。 miRNA降解的分子框架也可能适用于siRNA或PIRNA，这些siRNA或PIRNA成为赋予植物和动物表观遗传记忆的药物，从而进一步扩大了工作的影响。