Small RNA Pathways in Mammalian Gametogenesis

基础和临床研究表明，各种非编码 RNA 和小 RNA 发挥着重要且多样化的作用 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元件的影响。事实上，哺乳动物的胚芽 已知细胞具有多种小 RNA 种类，包括小干扰 RNA (siRNA)、microRNA (miRNA) 和种系特异性 PlWI 相互作用 RNA (piRNA)。然而，它们的机械作用 配子发生和人类不育在很大程度上尚不明确。康奈尔生殖中心 Genomics (CRG) 成立于 2006 年，在小 RNA 生物学领域发展了新兴优势 来解决我们理解中的这些差距。这些研究的目的是阐明小RNA的作用 产生可行的整倍体配子的事件中的途径。提议四个项目： 项目 I（PI： Andrew Crimson）将定义小 RNA 表达和小 RNA 靶标的时间概况 在整个精子发生过程中，重点关注小鼠前期 I 的开始和进展； 项目 II（负责人：Darius Paduch）将探索 microRNA 在人类男性生殖细胞中的作用和表达 和体细胞区室，并将检查不育症患者睾丸小 RNA 谱的变化 男人；项目 III（PI：Paula Cohen）将探索 Argonaute 家族在小 RNA 结合中的作用 小鼠减数分裂前期 I 沉默关键过程中的蛋白质；和项目 IV（PI：John Schimenti）将研究如何控制哺乳动物生殖细胞中 DNA 复制许可的过程 通过 microRNA、miR34 介导的转录后控制。建议设立三个核心： 行政管理 核心、Outreach 核心和 RNA 测序核心，后者向所有 SCCPIR 成员开放。 总的来说，这些研究代表了对小RNA通路最全面的分析 迄今为止，哺乳动物配子发生，并将提供小RNA调控方面的尖端计划 这些流程将成为 SCCPIR 网络的独特且及时的补充。综合集中于 种系中小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健康配子的产生。

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.