Understanding Complex Genome Editing and RNA Biology in Oxytricha

了解尖毛虫中复杂的基因组编辑和 RNA 生物学

• 批准号: 10415638
• 负责人: LAURA F LANDWEBER
• 金额: $ 77.17万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10415638
• 关键词: Address; Adenine; Architecture; Biochemistry; Biological Models; Biology; Chromatin; Chromosomal Rearrangement; Complex; DNA; Development; Disease; Eukaryota; Event; Evolution; Frequencies; Functional disorder; Gene Rearrangement; Genes; Genetic; Genome; Genome Stability; Genomic Instability; Goals; Human; Inherited; Knowledge; Maintenance; Malignant Neoplasms; Methylation; Molecular; Molecular Genetics; Organism; Oxytricha; Pathway interactions; Process; Public Health; RNA; RNA Editing; RNA Processing; RNA-Binding Proteins; Research; Role; System; Tumor Suppressor Genes; Untranslated RNA; Variant; chimeric gene; comparative genomics; genetic architecture; genome editing; genome integrity; human disease; insight; microbial; overexpression; tool; tumor

Understanding Complex Genome Editing and RNA Biology in Oxytricha Project Summary/Abstract: The PI’s lab studies natural genome editing systems in microbial eukaryotes, bringing a strongly molecular and mechanistic approach to understanding genome evolution and diversity. The surprisingly sophisticated variations on DNA and RNA processing in microbial eukaryotes display a wide range of genome architectures and genetic systems. Some pathways erode the notions of a gene (e.g. scrambled genes and RNA editing) and even Mendelian inheritance, reminding us that a draft genome sequence can be a far cry from knowledge of its products. Genome rearrangements occur in diverse organisms, and contribute to many human diseases, especially cancer—a disease of the genome, but the extreme level of programmed DNA rearrangements required for development in the ciliate Oxytricha make it an ideal model system to study genome remodeling and the roles of RNA in orchestrating this process. The proposed research will expand the lab’s focus on the molecular mechanisms and evolution of this remarkable natural phenomenon. Goals for the next five years include understanding the roles of DNA N6-adenine methylation (6mA) during development and rearrangement, and the interactions between small and long noncoding RNAs and their associated RNA- binding proteins, together with the rearranging genome. Tools from molecular genetics, biochemistry, and chromatin biology provide the platform for functional studies, while comparative genomics offers insight into the evolutionary origins of scrambled genomes and complex genetic architectures, addressing the fundamental questions of how programmed rearrangements are executed during development and how this process arose during evolution.

理解尖毛藻的复杂基因组编辑和RNA生物学 项目概要/摘要： PI的实验室研究微生物真核生物中的天然基因组编辑系统， 分子和机制的方法来理解基因组的进化和多样性。令人惊讶的 微生物真核生物中DNA和RNA加工的复杂变化显示了广泛的基因组 结构和遗传系统。一些途径削弱了基因的概念（例如，乱序基因和 RNA编辑）甚至孟德尔遗传，提醒我们基因组序列草图可能与 了解其产品。基因组重排发生在不同的生物体中， 人类疾病，特别是癌症-一种基因组疾病，但编程DNA的极端水平 纤毛类Oxytricha的发育所需的重排使其成为研究的理想模式系统 基因组重塑和RNA在协调这一过程中的作用。拟议的研究将扩大 该实验室的重点是分子机制和这一显着的自然现象的演变。目标 接下来的五年包括了解DNA N6-腺嘌呤甲基化（6 mA）在发育过程中的作用 和重排，以及小的和长的非编码RNA与它们相关的RNA之间的相互作用- 结合蛋白，以及重组基因组。分子遗传学、生物化学和 染色质生物学为功能研究提供了平台，而比较基因组学则提供了对 混乱的基因组和复杂的遗传结构的进化起源，解决 如何在发展过程中执行程序化的重排，以及这是如何实现的基本问题。 在进化过程中产生的。