RNA-based Mechanisms Specifying Heritable Epigenetic Change

现代遗传学和进化生物学是建立在孟德尔遗传的原则上的。这些原则概念化的个别因素负责遗传性状作为静态实体组成的DNA序列，携带在染色体上和性传播给后代。这种关于遗传的观点与过去世纪的大多数实验研究都很吻合。然而，从一代到下一代，某些特质因素表现出动态但可预测的变化的特殊行为长期以来一直表明，遗传的其他原则仍有待发现。该项目研究了玉米植物中发生的非孟德尔表观遗传形式。表观遗传是指遗传信息，是附件的DNA，遗传的主要分子。最近的研究表明，小RNA分子和一些负责从DNA模板合成RNA的酶（RNA聚合酶）是这种非孟德尔遗传的致病因子。RNA聚合酶的形式和它们在玉米中的功能的多样性特别广泛。最初的研究指出，在很大程度上未探索的不同的RNA聚合酶共享的亚基蛋白质的关系，具有潜在的调控意义的基因组功能。该项目将表征玉米基因组中所有RNA聚合酶的多蛋白结构和机械功能，从而开发一个模型系统，用于理解RNA聚合酶多样性在高度重复的真核基因组中的基本作用。所产生的工具和材料将用于表征农业上重要的作物物种中RNA聚合酶的复杂性和功能，并测试有关这种基于RNA的机制的特定假设，该机制负责指定可遗传的表观遗传变化。本项目生产特定植物种质材料、生物信息资源、和实验试剂，使长期的社区努力，以了解DNA依赖的RNA聚合酶的作用，和小RNA分子，在定义表观基因组中起作用--DNA或相关染色体结构的修改，指定了基因组编码信息的读数。研究活动提供教育和培训生殖生物学，遗传，孟德尔和传递遗传学，遗传分析，染色体生物学，和现代分子遗传学的一个加州伯克利大学（UCB）的研究生，至少两个UCB本科生，和高中学生从加州东湾地区。传统上在科学领域代表性不足的少数民族通过现有的高中和本科研究计划的支持参与这些研究活动，促进种族和社会经济多样性。在这个项目中研究的非孟德尔遗传的具体例子会影响色素沉着基因，因此在概念上很容易传达给不同的观众，因为所涉及的特征是熟悉和视觉的。了解真核遗传学的这种特殊机制为基于RNA的遗传提供了一个新的视角，有望对从结构生物学到进化的广泛学科的未来生物学研究产生变革性影响。

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.