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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

基本信息

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
项目类别：
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

项目摘要

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.

项目总结