Small RNA Pathways in Mammalian Gametogenesis

哺乳动物配子发生中的小 RNA 通路

• 批准号: 9250640
• 负责人: Paula Elaine Cohen
• 金额: $ 146万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-14 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9250640
• 关键词: Address; Applications Grants; Area; Basic Science; Biology; Clinical Research; Conceptions; DNA Damage; DNA Sequencing Facility; DNA Transposable Elements; DNA biosynthesis; Development; Ensure; Event; Family; Fertility; Functional disorder; Gametogenesis; Gene Expression Regulation; Genetic Transcription; Genome; Genomics; Germ Cells; Goals; Human; Infertility; Instruction; Mediating; Meiosis; Meiotic Prophase I; MicroRNAs; Mus; Pathway interactions; Play; Post-Transcriptional Regulation; Process; Production; RNA-Binding Proteins; Replication Licensing; Reproduction; Role; Small Interfering RNA; Small RNA; Spermatogenesis; Time; Transcriptional Regulation; Untranslated RNA; comparative; egg; human male; member; men; outreach; programs; reproductive; response; sperm cell; transcriptome sequencing

Basic and clinical research is revealing that various noncoding and small RNAs play important and diverse roles in germ cell development and quality, including X/Y silencing during meiosis, gene regulation, DNA damage responses, and protection of the genome against transposable elements. Indeed, mammalian germ cells are known to hart)or multiple small RNA species, including small interfering RNAs (siRNA), microRNAs (miRNA), and germline-specific PlWI-interacting RNAs (piRNA). However, their mechanistic roles in gametogenesis and human infertility are largely uncharacterized. The Cornell Center for Reproductive Genomics (CRG), established in 2006, has developed emerging strengths in the area of small RNA biology to address these gaps in our understanding. The goal of these studies is to elucidate the role of small RNA pathways in the events that give rise to viable euploid gametes. Four projects are proposed: Project I (PI: Andrew Crimson) will define the temporal profile of small RNA expression and small RNA targets throughout spermatogenesis, focusing on the onset of, and progression through, prophase I in the mouse; Project II (PI: Darius Paduch) will explore the roles and expression of microRNAs in human male germ cell and somatic compartments, and will examine changes in the profiles of testicular small RNAs In infertile men; Project III (PI: Paula Cohen) will explore the role of the Argonaute family of small RNA binding proteins in the critical process of meiotic silencing during prophase I in mice; and Project IV (PI: John Schimenti) will examine how the process of DNA replication licensing in mammalian germ cells is controlled by post-transcriptional control mediated by microRNA, miR34. Three cores are proposed: an Administrative core, and Outreach Core and an RNA sequencing core, the latter being open to all SCCPIR members. Collectively, these studies represent the most comprehensive analysis of small RNA pathways in mammalian gametogenesis to date, and will provide a cutting-edge program in small RNA regulatory processes that will be a unique and timely addition to the SCCPIR network. The combined focus on comparative analysis of small RNA pathways in the germline is likely to contribute greatly to the understanding of how these pathways may function to ensure the production of healthy gametes.

基础和临床研究表明，各种非编码和小RNA发挥着重要和多样化的作用 在生殖细胞发育和质量中的作用，包括减数分裂过程中的X/Y沉默，基因调控，DNA 损伤反应，以及保护基因组免受转座因子的影响。事实上，哺乳动物的生殖器 细胞已知为HART)或多种小RNA物种，包括小干扰RNA(SiRNA)、microRNA (MiRNA)和生殖系特异性PlWI相互作用RNAs(PiRNA)。然而，他们在这方面的机械作用 配子发生和人类不孕不育在很大程度上还没有定论。康奈尔生殖中心 基因组学(CRG)成立于2006年，在小RNA生物学领域形成了新的优势 以解决我们在理解上的这些差距。这些研究的目的是阐明小RNA的作用 在产生可行整倍体配子的事件中的途径。提出了四个项目：项目I(PI： Andrew Crimson)将定义小RNA表达和小RNA靶标的时间分布 在整个精子发生过程中，重点放在小鼠第一阶段前期的开始和进展； 项目II(PI：Darius Paduch)将探索microRNAs在人类男性生殖细胞中的作用和表达 和体细胞室，并将检查不育患者睾丸小RNA图谱的变化 人类；项目III(PI：Paula Cohen)将探索ArgAerte家族的小RNA结合的作用 小鼠减数分裂前期沉默关键过程中的蛋白质；和项目IV(PI：John Schimenti)将研究哺乳动物生殖细胞中的DNA复制许可过程是如何控制的 通过microRNA介导的转录后调控，miR34。提出了三个核心：管理 核心、外联核心和核糖核酸测序核心，后者对SCCPIR的所有成员开放。 总的来说，这些研究代表了对小RNA途径的最全面的分析 到目前为止，哺乳动物配子发生，并将提供一个尖端的小RNA调节程序 这些进程将成为SCCPIR网络的一项独特和及时的补充。合并后的重点是 对生殖系中小RNA途径的比较分析可能对 了解这些途径如何发挥作用，以确保产生健康的配子。