Mechanisms governing floral stem cell maintenance and miRNA functions in Arabidop

拟南芥花干细胞维持和 miRNA 功能的调控机制

• 批准号: 7884034
• 负责人: Xuemei Chen
• 金额: $ 30.51万
• 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 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7884034
• 关键词: Address; Animals; Arabidopsis; Biogenesis; Biological Process; Biology; Cell Maintenance; Cells; Cues; Development; Developmental Biology; Developmental Process; Equilibrium; Family; Flowers; Funding; Future; Gene Expression; Gene Expression Regulation; Gene Targeting; Genes; Goals; Heart; Laboratories; Lead; Light; Maintenance; Mediating; Meristem; MicroRNAs; Molecular; Mouse-ear Cress; Organ; Organism; Physiology; Plant Genes; Plant Model; Plants; Pluripotent Stem Cells; Polycomb; Process; Proteins; Regenerative Medicine; Regulation; Regulator Genes; Research; Role; Small Interfering RNA; Small RNA; Staging; Stem cells; System; Transcription factor genes; Translational Repression; Work; base; cell fate specification; fighting; histone modification; human disease; insight; interest; mRNA Transcript Degradation; novel; pathogen; public health relevance; stem cell biology; stem cell fate; transcription factor

DESCRIPTION (provided by applicant): A fundamental question in developmental biology is how pluripotent stem cells are maintained and how they differentiate into various lineages in multicellular organisms. Flower development in the model plant Arabidopsis thaliana offers a great system to address key questions in stem cell biology. One of our long-term goals is to uncover the mechanisms that govern the maintenance and termination of floral stem cells. We and others have uncovered an as yet incomplete network of three transcription factors superimposed by a microRNA (miRNA)-based posttranscriptional mechanism that governs the maintenance of floral stem cells. In the proposed research, we will expand this network by identifying core components at the heart of floral stem cell regulation. We will 1) identify target genes of the two key transcription factors, 2) incorporate the newly identified floral stem cell regulators, ARF2, ARF3 and ARF4, and the small RNA that regulates the three transcription factor genes into the existing framework of floral stem cell regulation, and 3) probe the role of the Polycomb group proteins in floral stem cell termination. miRNAs are sequence-specific regulatory molecules that impact numerous biological processes including development. The trans-acting siRNAs (ta-siRNAs) are a class of plant-specific, miRNA-like small RNAs with important developmental roles. Another long-term research goal is to dissect the general mechanisms underlying the biogenesis and mode of action of small RNAs and to study how the biogenesis or activities of specific miRNAs or ta-siRNAs are modulated in development. Whereas the major framework of miRNA biogenesis is established, how miRNAs inhibit target gene expression is highly controversial at present. The field is at its very early stages of understanding how the activities of specific small RNAs are regulated in developmental contexts. A key to dissecting the mode of action of miRNAs and understanding how small RNA activity is regulated in development is to identify proteins that mediate or modulate the activities of small RNAs. We have identified two such proteins, AGO10 and AMP1 in small RNA-mediated target gene regulation. The proposed research is aimed at uncovering the molecular functions of these two proteins. The proposed work will undoubtedly provide novel insights into stem cell regulation and miRNA function. Understanding how stem cells are maintained and terminated in plants will help derive basic principles that govern stem cell biology and contribute to the ultimate use of stem cells in regenerative medicine. Due to the highly conserved mechanisms underlying miRNA biogenesis and function between plants and animals, an advance in the mechanistic understanding of miRNA function from our work will directly impact our abilities to harness the power of small RNAs to fight pathogens and human diseases. PUBLIC HEALTH RELEVANCE: Understanding how stem cells are maintained and how they differentiate is key to harnessing the power of stem cells for regenerative medicine in the future. This research will reveal major players in the transcriptional and post-transcriptional networks that govern the temporal regulation of stem cells. This research will also advance our understanding of the mode of action of miRNAs, regulatory molecules that impact all aspects of biology and whose mis-regulation is associated with human diseases.

描述(申请人提供)：发育生物学中的一个基本问题是如何维持多潜能干细胞，以及它们如何在多细胞生物体中分化为不同的谱系。模式植物拟南芥的花发育为解决干细胞生物学中的关键问题提供了一个很好的系统。我们的长期目标之一是揭示支配花干细胞维持和终止的机制。我们和其他人已经发现了一个尚不完整的网络，由三个转录因子组成，其中叠加了一个基于microRNA(MiRNA)的转录后机制，该机制管理花干细胞的维持。在这项拟议的研究中，我们将通过确定花干细胞调控的核心成分来扩大这一网络。我们将1)确定两个关键转录因子的靶基因，2)将新发现的花干细胞调控因子ARF2、ARF3和ARF4以及调节这三个转录因子基因的小RNA整合到现有的花干细胞调控框架中，3)探讨Polycomb组蛋白在花干细胞终止中的作用。MiRNAs是序列特异的调节分子，影响包括发育在内的许多生物过程。反式作用siRNAs(ta-siRNAs)是一类植物特有的类似miRNA的小RNA，具有重要的发育作用。另一个长期的研究目标是剖析小RNA的生物发生和作用模式的一般机制，并研究特定的miRNAs或ta-siRNAs的生物发生或活动在发育过程中是如何调节的。虽然miRNA生物发生的主要框架已经建立，但目前miRNAs如何抑制靶基因表达仍存在很大争议。该领域正处于非常早期的阶段，了解特定小RNA的活动是如何在发育背景下受到调节的。要剖析miRNAs的作用模式并了解小RNA活性在发育过程中是如何调节的，关键是要识别介导或调节小RNA活动的蛋白质。我们已经在小RNA介导的靶基因调控中发现了两个这样的蛋白质，AGO10和AMP1。这项拟议的研究旨在揭示这两种蛋白质的分子功能。这项拟议的工作无疑将为干细胞调控和miRNA功能提供新的见解。了解干细胞是如何在植物中维持和终止的，将有助于得出管理干细胞生物学的基本原则，并有助于干细胞在再生医学中的最终使用。由于miRNA的生物发生和功能在植物和动物之间具有高度保守的机制，我们工作中对miRNA功能的机制理解的进展将直接影响我们利用小RNA的力量对抗病原体和人类疾病的能力。 与公共卫生相关：了解干细胞是如何维持和分化的，是未来利用干细胞的力量用于再生医学的关键。这项研究将揭示控制干细胞时间调控的转录和转录后网络的主要参与者。这项研究还将促进我们对miRNAs作用模式的理解，miRNAs是影响生物学各个方面的调控分子，其错误调控与人类疾病有关。