Understanding Complex Gene Editing Systems and RNA Biology in Oxytricha

了解尖毛虫中复杂的基因编辑系统和 RNA 生物学

• 批准号: 10198942
• 负责人: LAURA F LANDWEBER
• 金额: $ 72.49万
• 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 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10198942
• 关键词: Address; Architecture; Biological Models; Biology; Chromatin; Chromosomal Rearrangement; Complex; DNA; Dependence; Development; Disease; Distant; Epigenetic Process; Eukaryota; Event; Evolution; Frequencies; Gene Rearrangement; Genes; Genetic; Genetic Recombination; Genome; Genome Stability; Genomic Instability; Goals; Human; Inherited; Knowledge; Light; Maintenance; Malignant Neoplasms; Molecular; Molecular Genetics; Organism; Oxytricha; Pathway interactions; Process; Public Health; RNA; RNA Biochemistry; RNA Editing; RNA Processing; RNA Splicing; Research; Role; System; Tumor Suppressor Genes; Untranslated RNA; Variant; cancer genome; chimeric gene; chromothripsis; comparative genomics; genetic architecture; genome integrity; human disease; insight; microbial; novel; overexpression; tool; tumor

Understanding Complex Gene Editing Systems and RNA Biology in Oxytricha Project Summary/Abstract: The PI's lab studies novel genetic 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 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 and dependence on chromosomal rearrangements for correct development in the ciliate Oxytricha make it an ideal model system to study genome remodeling and the roles of RNA in epigenetic control of this process. The proposed research will focus on understanding the molecular mechanism and evolutionary origin of this remarkable phenomenon. Goals for the next five years include obtaining a more detailed understanding of the interactions between small and long noncoding RNAs, both with each other and together with the rearranging genome. Tools from molecular genetics, RNA biochemistry, and chromatin biology provide the platform for functional studies, while comparative genomics of closely and more distantly related species will provide insight into the evolutionary origins of scrambled genomes and complex genetic architectures in the Oxytricha lineage, addressing the basic questions of how they rearrange during development and how they arose during evolution.

了解氧气中的复杂基因编辑系统和RNA生物学 项目摘要/摘要： PI的实验室研究微生物真核生物中的新遗传系统，带来了强烈的分子和 理解基因组进化和多样性的机械方法。令人惊讶的精致 微生物真核生物中DNA和RNA加工的变化显示了广泛的基因组架构 和遗传系统。一些途径侵蚀了基因的音符（例如，炒基因和RNA编辑） 甚至孟德尔的继承，提醒我们，基因组序列与对 它的产品。基因组重排发生在潜水生物中，并导致许多人类疾病， 尤其是癌症 - 一种基因组疾病，但编程的DNA重排的极端水平和 依赖染色体重排以正确发育的纤毛氧气使其成为 研究基因组重塑的理想模型系统以及RNA在该过程表观遗传控制中的作用。 拟议的研究将着重于理解这一点的分子机制和进化起源 引人注目的现象。未来五年的目标包括获得对 小型和长期不编码的RNA之间的相互作用彼此以及与 重新排列基因组。分子遗传学，RNA生物化学和染色质生物学的工具提供了 功能研究平台，而密切相关的物种的比较基因组学将 提供有关炒基因组和复杂遗传体系结构的进化起源的见解 Oxytricha血统，解决了他们在开发过程中如何重新排列以及如何重新排列的基本问题 在进化过程中出现。