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.

获奖项目摘要/Abstract 转座子是一种多产的遗传寄生虫，其渗透超过45%的人类基因组，并且占主要比例。 所有动物的基因组。我们的实验室研究Piwi/皮尔纳途径，RNA干扰（RNAi）的一个分支， 系统，识别和沉默转座子转录，以保持基因组的稳定性和生育力。我们实验室 专门研究转座子和Piwi/皮尔纳通路之间的相互作用和动力学， 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和转座子之间的调控机制，我们 在Piwi/皮尔纳通路上部署基因组学、生物化学和小RNA分析方法。 该项目的主要重点是研究超移动Har-P元件转座子变体， 发现的是P-转座酶的弹药，以驱动性腺发育不全（GD）的不育综合征， 果蝇我们的项目的优势依赖于独特的果蝇品系和细胞系分析， Lau实验室研究Har-P元件如何受piRNA调控，弗拉门戈皮尔纳的增强子如何 簇可以从Har-P元件产生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， Har-P-元件变体的父系沉默机制，这是一种驱动严重GD的超移动转座子。 目的2：研究来自Flamenco皮尔纳簇的P元件piRNA的转录调控 以及皮尔纳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 深入了解转座子调控，产生新的研究试剂和工具，用于研究生育综合征 GD，并告知由piRNA介导的跨代表观遗传过程。