The interplay between transposons and piRNA pathways.

转座子和 piRNA 通路之间的相互作用。

• 批准号: 10611843
• 负责人: NELSON C LAU
• 金额: $ 40.4万
• 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 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10611843
• 关键词: Affect; Animals; Biochemical; Biological Assay; Cell Line; Cells; Chromatin; DNA Transposons; Data; Daughter; Deposition; Drosophila genus; Elements; 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; Infiltration; Insecta; Introns; Knowledge; Learning; Link; Luciferases; Malignant Neoplasms; Mediating; Ovarian; Parasites; Pathway interactions; Production; Proliferating; Pupa; RNA Interference; RNA Splicing; Reagent; Regulation; Regulatory Element; Reporter; Reporter Genes; 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; transmission process

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.

项目概要/摘要 转座子是一种多产的遗传寄生虫，渗透到人类基因组的 45% 以上，并且占主要比例 我们的实验室研究了 Piwi/piRNA 通路（RNA 干扰 (RNAi) 的一个分支）的作用。 系统，识别并沉默转座子转录本以保持基因组稳定性和生育力。 专门研究转座子和 Piwi/piRNA 通路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对动物健康产生负面影响的目标。 为了从根本上揭示动物基因组与转座子之间的调控机制，我们正在 在 Piwi/piRNA 通路上部署基因组学、生化和小 RNA 分析方法。 该项目的主要重点是研究我们的超移动 Har-P 元件转座子变体 发现了 P-转座酶的弹药来驱动性腺发育不全（GD）的不孕综合症 我们项目的优势依赖于独特的果蝇菌株和细胞系检测。 刘实验室研究piRNA如何调节Har-P元素，以及弗拉门戈piRNA的增强子如何调节 簇可以从 Har-P 元件生成 piRNA，以及 Har-P piRNA 如何调节内含子剪接。 本项目将实现以下目标： 目标 1：确定动员能力和 Har-P-element 变体的父系沉默机制，一种可驱动严重 GD 的超机动转座子。 目标 2：剖析来自弗拉门戈 piRNA 簇的 P 元件 piRNA 的转录调控 以及 piRNA 沉默和内含子剪接抑制之间的机制联系，该项目将产生新的成果。 深入了解转座子调控，产生用于研究生育综合症的新研究试剂和工具 GD 的研究，并提供有关 piRNA 介导的跨代表观遗传过程的信息。