Role of microtubules in the non-cell autonomous activities of plant microRNAs

微管在植物 microRNA 非细胞自主活动中的作用

• 批准号: 10237371
• 负责人: Xuemei Chen
• 金额: $ 31.1万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-05 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10237371
• 关键词: Affect; Animals; Arabidopsis; Area; Biochemical; Biogenesis; Biological; Biological Process; Biology; Cell Communication; Cell physiology; Cells; Collection; Cytoskeleton; Defect; Development; Developmental Process; Endoplasmic Reticulum; Enzymes; Eukaryota; Foundations; Future; Gene Expression; Genes; Genetic Screening; Genomic approach; Human; Investigation; Knowledge; Lead; Light; Link; Mediating; MicroRNAs; Microtubules; Modeling; Molecular; Movement; Nature; Organ; Organism; Other Genetics; Pattern; Personal Satisfaction; Physiological; Plant Diseases; Plant Model; Plant Roots; Plants; Process; Proteins; RNA; RNA Interference; Regulation; Regulator Genes; Repression; Research; Resolution; Resources; Role; Signal Transduction; Small Interfering RNA; Small RNA; Source; Therapeutic Agents; Tissues; Translations; Travel; base; cell type; extracellular vesicles; genetic manipulation; genetic resource; tool; trafficking

PROJECT SUMMARY microRNAs (miRNAs) are sequence-specific regulators of gene expression that impact almost all biological processes in diverse eukaryotes. Defects in miRNA-based regulation lead to developmental and physiological abnormalities in both plants and animals. Thanks to nearly two decades of research, the molecular machinery responsible for miRNA biogenesis and modes of action has been uncovered. However, since most biochemical studies on miRNAs or related small interfering RNAs were performed with cell-free extracts, how the small RNA machinery interplays with the cytoskeleton remains largely unknown. Historically, miRNAs are viewed as cell-autonomous regulatory molecules, but in recent years, mounting evidence points to the existence of miRNAs in extracellular vesicles in animals as well as the movement of miRNAs between cells in plants. Despite accumulating evidence implicating miRNAs as informational molecules in cell-cell communications, the scope of biologically significant, non-cell autonomous activities of miRNAs is largely unknown, let alone the molecular mechanisms that enable, constrain, or regulate the non-cell autonomy of miRNAs. The project interrogates the scope of miRNAs serving as informational molecules in cell-cell communications and investigates the mechanisms underlying the non-cell autonomous activities of miRNAs using the Arabidopsis model. In addition to sophisticated tool sets as available resources, advantages offered by the Arabidopsis model include the well-documented, non-cell autonomous activities of a few miRNAs in intact plants and the ease to perform forward genetic screens that do not require any a priori assumptions regarding the cellular machinery for miRNA’s non-cell autonomy. A forward genetic screen from the PI’s group revealed a previously unsuspected link between microtubules and the non-cell autonomous activities of miRNAs as well as a tantalizing connection between the translation repression activities of miRNAs and their non-cell autonomous activities. The project takes advantage of the layered cell organization in roots and employs genomics approaches at single-cell-layer resolution to study how microtubules enable the non-cell autonomous activities of miRNAs. By elucidating the scope of miRNA’s non-cell autonomy, the project has the potential to change the dogma that miRNAs largely act cell-autonomously and set the paradigm that miRNAs serve as signals in cell- cell communications. Through pioneering efforts to interrogate mechanisms underlying the non-cell autonomous activities of miRNAs, the project will provide initial knowledge in this largely unknown territory and set the foundation for future studies. By revealing a role of the cytoskeleton in small RNA biology, the impacts of the project will reach beyond plant biology.

项目摘要 microRNA（miRNA）是基因表达的序列特异性调节剂，几乎影响所有生物学 潜水员真核生物的过程。基于miRNA的调节缺陷导致发育和生理 植物和动物的异常。感谢近二十年的研究，分子机械 负责miRNA生物发生和作用模式。但是，由于大多数生化 用无细胞提取物进行了有关miRNA或相关小干扰RNA的研究，小型 RNA机械与细胞骨架的相互作用在很大程度上未知。从历史上看，miRNA被视为 细胞自主的调节分子，但近年来，山的证据表明存在 动物细胞外蔬菜的miRNA以及植物中细胞之间miRNA的运动。 尽管积累了证据隐式miRNA作为细胞 - 细胞通信中的信息分子，但 miRNA的生物学意义，非细胞自主活动的范围在很大程度上是未知的，更不用说 能够启用，约束或调节miRNA的非细胞自主权的分子机制。 该项目询问了在细胞细胞中用作信息分子的miRNA的范围 通信和研究miRNA的非电池自主活动的基础机制 使用拟南芥模型。除了可用资源的复杂工具集外，还提供了优势 通过拟南芥模型包括一些有据可查的非细胞自主活动 完整的植物以及不需要任何先验假设的前向遗传筛选 关于miRNA的非细胞自治的细胞机械。 PI小组的前遗传屏幕 揭示了微管与非单元自主活动之间的先前未跨性别的联系 miRNA以及miRNA及其翻译表达活动之间的诱人联系 非电池自主活动。该项目利用了根源的分层单元组织 员工基因组学以单细胞层分辨率方法研究微管如何启用非细胞 miRNA的自主活动。 通过阐明miRNA的非细胞自治的范围，该项目有可能改变 miRNA在很大程度上作用于细胞自主的教条，并设置了miRNA作为细胞中信号的范式 细胞通信。通过开创性的努力来审问非细胞的基础机制 miRNA的自主活动，该项目将在这个很大程度上未知的领土上提供初始知识， 为未来的研究奠定了基础。通过揭示细胞骨架在小RNA生物学中的作用，影响 该项目将超越植物生物学。