RNA-based Mechanisms Specifying Heritable Epigenetic Change

基于 RNA 的机制指定可遗传的表观遗传变化

• 批准号: 0920623
• 负责人: Jay Hollick
• 金额: $ 49.68万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0920623&HistoricalAwards=false
• 关键词: RNA; based; Mechanisms; Specifying; Heritable

Modern genetics and evolutionary biology are founded on the principles of Mendelian inheritance. These principles conceptualize the individual factors responsible for inherited traits as static entities comprised of DNA sequences that are borne on chromosomes and sexually transmitted to offspring. This view of inheritance conforms well to most experimental studies of the past century. However, exceptional behaviors in which certain trait factors display dynamic, yet predictable, changes from one generation to the next have long indicated that additional principles of inheritance remain to be discovered. This project investigates a form of non-Mendelian epigenetic inheritance occurring in the corn plant. Epigenetic refers to heritable information that is accessory to DNA, the primary molecule of inheritance. Recent studies indicate that both small RNA molecules and some of the enzymes responsible for synthesizing RNA from DNA templates (RNA polymerases) are causative agents in this type of non-Mendelian inheritance. The diversity of both RNA polymerase forms and their functions in corn is particularly extensive. Initial studies point to largely unexplored relationships of the subunit proteins shared by diverse RNA polymerases that have potential regulatory significance to genome function. This project will characterize both the multiprotein structures and mechanistic functions of all RNA polymerases of the corn genome and thereby develop a model system for understanding the fundamental roles of RNA polymerase diversity in a highly repetitive eukaryotic genome. The tools and materials generated will be used to characterize the complexity and function of RNA polymerases in an agriculturally important crop species and to test specific hypotheses regarding this RNA-based mechanism responsible for specifying heritable epigenetic changes.Broader Impacts: This project produces specific plant germplasm materials, bioinformatics resources, and experimental reagents that enable a long-term community effort to understand the roles that DNA-dependent RNA polymerases, and small RNA molecules, play in defining the epigenome -- modifications of the DNA or associated chromosome structure that specify readouts of genome-encoded information. The research activities provide education and training in reproductive biology, inheritance, Mendelian and transmission genetics, genetic analysis, chromosome biology, and modern molecular genetics for one University of California Berkeley (UCB) graduate student, at least two UCB undergraduates, and high school students from the California East Bay area. Minorities traditionally underrepresented in the sciences are engaged in these research activities through the support of existing high school and undergraduate research programs promoting ethnic and socioeconomic diversity. The specific example of non-Mendelian inheritance studied in this project affects a pigmentation gene and is therefore conceptually easy to convey to a diverse audience because the trait involved is familiar and visual. Understanding this particular mechanism of eukaryotic genetics provides a novel perspective of RNA-based inheritance promising transformative impacts to the future of biological research across broad disciplines from structural biology to evolution.

现代遗传学和进化生物学是建立在门德尔继承原则的基础上的。这些原则将负责遗传性状的个体因素概念化为静态实体，该静态实体由染色体上的DNA序列组成，并将其性传播给后代。这种继承的观点非常符合上个世纪的大多数实验研究。但是，某些特征因素表现出动态但可预测的从一代到下一代的变化的特殊行为长期以来表明遗传的其他原理仍有待发现。该项目调查了玉米植物中发生的一种非孟德尔表观遗传遗传的形式。表观遗传学是指遗传性信息，该信息是DNA的附件，DNA是继承的主要分子。最近的研究表明，小的RNA分子和某些负责从DNA模板（RNA聚合酶）合成RNA的酶都是这种非孟德尔遗传的致病药物。两种RNA聚合酶形式的多样性及其在玉米中的功能尤其广泛。最初的研究表明，不同的RNA聚合酶共享的亚基蛋白的关系在很大程度上未开发，这些蛋白质对基因组功能具有潜在的调节意义。该项目将表征玉米基因组所有RNA聚合酶的多蛋白结构和机械功能，从而开发出一种模型系统，以理解RNA聚合酶多样性在高度重复性的真核基因组中的基本作用。生成的工具和材料将用于表征农业重要的农作物中RNA聚合酶的复杂性和功能，并测试有关该基于RNA的机制的特定假设聚合酶和小RNA分子在定义表观基因组 - DNA或相关染色体结构的修饰方面发挥作用，这些染色体结构指定了基因组编码信息的读数。研究活动为加州一名伯克利大学（UCB）的一名研究生，至少两名UCB大学生以及来自加利福尼亚州东湾地区的高中生提供了有关生殖生物学，遗传，孟德尔和传播遗传学，遗传分析，遗传分析，染色体生物学和现代分子遗传学的教育和培训。传统上，科学中的少数群体通过支持现有的高中和本科研究计划，从事这些研究活动，从而促进了种族和社会经济多样性。该项目中研究的非孟德尔继承的具体例子会影响着色素沉着的基因，因此在概念上很容易传达给多样化的受众，因为所涉及的特征是熟悉和视觉的。理解这种真核遗传学的这种特殊机制为基于RNA的遗产提供了一种新颖的观点，这对从结构生物学到进化的广泛学科的生物学研究产生了有希望的变革性影响。