The interplay between transposons and piRNA pathways

转座子和 piRNA 通路之间的相互作用

• 批准号: 10392705
• 负责人: NELSON C LAU
• 金额: $ 0.97万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-10 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10392705
• 关键词: Affect; Animals; Award; Biochemical; Biological Assay; Cell Line; Chromatin; DNA Transposons; Data; Daughter; Deposition; Drosophila genus; Embryo; Enhancers; Epigenetic Process; Female infertility; Fertility; Fertility Study; Genetic; Genetic Enhancer Element; Genetic study; Genome; Genome Stability; Genomics; Goals; Gonadal Dysgenesis; Health; Human; Human Genome; Hybrids; Infertility; Infertility study; Insecta; Introns; Knowledge; Learning; Link; Luciferases; Malignant Neoplasms; Mediating; Ovarian; Parasites; Pathway interactions; Phosphorus; Production; Proliferating; Pupa; RNA Interference; RNA Splicing; Reagent; Regulation; Regulatory Element; Reporter; Research; Role; Small RNA; Syndrome; System; Testing; Testis; Transcript; Transcriptional Regulation; Transcriptional Silencer Elements; Transgenic Organisms; Transposase; Validation; Variant; arm; cellular development; chromosomal location; epigenetic silencing; experimental study; female fertility; fly; genome integrity; insight; knock-down; male; negative affect; novel; piRNA; preservation; prevent; sperm cell; tool; transcription factor

Awarded Project Summary/Abstract Transposons are prolific genetic parasites infiltrating >45% of the human genome and are major proportions of all animal genomes. Our lab studies how the Piwi/piRNA pathway, an arm of the RNA interference (RNAi) system, recognizes and silences transposon transcripts to preserve genome stability and fertility. Our lab specializes in examining the interplay and dynamics between transposons and the Piwi/piRNA pathway with the goal of learning better how to prevent transposons from proliferating and negatively affecting animal health. To fundamentally uncover the regulatory mechanisms between animal genomes and transposons, we are deploying genomics, biochemical and small RNA analytical approaches on the Piwi/piRNA pathway. The major focus of this project is to study a hyper-mobile Har-P-element transposon variant that we discovered is the ammunition for P-transposase to drive the infertility syndrome of gonadal dysgenesis (GD) in Drosophila. Our project’s advantage relies on unique Drosophila strains and cell line assays developed in the Lau lab to study how the Har-P-element is regulated by piRNAs, how the enhancer of the Flamenco piRNA cluster can generate piRNAs from Har-P-elements, and how do Har-P piRNAs regulate intron splicing. This project will achieve the following aims in this project: Aim 1: Determine the mobilization capacity and paternal silencing mechanism of the Har-P-element variant, a hypermobile transposon that drives severe GD. Aim 2: Dissect the transcriptional regulation of P-element piRNAs coming from the Flamenco piRNA cluster and the mechanistic link between piRNA silencing and intron splicing inhibition. This project will yield new insight into transposon regulation, generate new research reagents and tools for studying the fertility syndrome of GD, and inform on transgenerational epigenetic processes mediated by piRNAs.

授予项目摘要/摘要 转座是多产的遗传寄生虫浸润> 45％的人类基因组，是主要比例 所有动物基因组。我们的实验室研究了RNA干扰（RNAi）的PIWI/PIRNA途径如何 系统，识别和沉默的转座子转录本以保持基因组稳定性和生育能力。我们的实验室 专门研究转座子与Piwi/Pirna途径之间的相互作用和动态 更好地学习如何防止转座子增殖和负面影响动物健康的目标。 为了从根本上揭示动物基因组和转座之间的调节机制，我们是 在PIWI/PIRNA途径上采用基因组学，生化和小RNA分析方法。 该项目的主要重点是研究我们的超模型har-p-元素转座子变体。 发现的是P-转座酶驱动性腺发育不全（GD）中的不孕综合征的弹药 果蝇。我们项目的优势依赖于独特的果蝇菌株和细胞系分析 LAU实验室研究HAR-P元素如何受PIRNA调节，Flamenco Pirna的增强剂如何 簇可以从HAR-P元素产生PIRNA，HAR-P PIRNA如何调节内含子剪接。 该项目将在该项目中实现以下目标：目标1：确定动员能力和 HAR-P元素变体的模式沉默机制，这是一种驱动严重GD的高速运动转座子。 AIM 2：剖析来自Flamenco Pirna群集的P元素PIRNA的转录调节 以及piRNA沉默与内含子剪接抑制之间的机械联系。这个项目将产生新的 深入了解转座子调节，生成新的研究试剂和研究生育综合征的工具 GD的信息，并告知由PIRNA介导的转化表观遗传过程。