Genetic and Molecular Dissection of Meiotic Silencing by Unpaired DNA

不配对 DNA 减数分裂沉默的遗传和分子解析

• 批准号: 0918937
• 负责人: Patrick Shiu
• 金额: $ 59.96万
• 依托单位: University of Missouri-Columbia
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0918937&HistoricalAwards=false
• 关键词: Genetic; Molecular; Dissection; Meiotic; Silencing

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).The overall goal of this project is to delineate the mechanism of Meiotic Silencing by Unpaired DNA (MSUD), a novel gene silencing system first described in Neurospora crassa. During the chromosome pairing stage, the zygotic cell examines the entire genome and compares the pairing of any DNA segment with its pairing partner. Any genes not paired with a similar sequence generates a silencing signal, which subsequently suppresses the gene expression of this unpaired DNA, as well as any sequences homologous to it, whether they are paired or not. Meiotic silencing utilizes the specific destruction of mRNA transcripts, a mechanism known as RNA interference (RNAi). The study of meiotic silencing will provide an excellent model for the delineation of the mechanism targeting unpaired DNA for silencing during meiosis, a process that could be important for imprinted X-chromosome inactivation and other phenomena in higher eukaryotes. Since RNAi has tremendous potential as an experimental tool to reveal gene functions, the understanding of meiotic silencing and other RNA-based silencing systems could have a broad impact on research in all areas of biology. Genetics, cell biology, and other approaches will be used to identify the machinery and the mechanistic steps required for the meiotic silencing system. Broader impact: The principal investigator is involved in a number of teaching and mentoring activities, such as the EXPRESS (Exposure to Research for Science Students) program. To broaden the participation of underrepresented groups, the investigators of this project will recruit and train undergraduate students from non-Ph.D.-granting and minority-serving institutions. A postdoctoral training plan with an emphasis on scholar preparation and mentoring/teaching skills will also be implemented.

该奖项根据 2009 年美国复苏和再投资法案（公法 111-5）提供资金。该项目的总体目标是描述不配对 DNA 减数分裂沉默 (MSUD) 的机制，这是一种首次在粗糙脉孢菌中描述的新型基因沉默系统。 在染色体配对阶段，合子细胞检查整个基因组，并将任何 DNA 片段与其配对伙伴的配对进行比较。 任何未与相似序列配对的基因都会产生沉默信号，随后抑制该未配对DNA以及与其同源的任何序列的基因表达，无论它们是否配对。 减数分裂沉默利用 mRNA 转录本的特异性破坏，这种机制称为 RNA 干扰 (RNAi)。 减数分裂沉默的研究将为描述减数分裂过程中针对未配对DNA进行沉默的机制提供一个极好的模型，减数分裂过程对于印记X染色体失活和高等真核生物中的其他现象可能很重要。 由于 RNAi 作为揭示基因功能的实验工具具有巨大的潜力，因此对减数分裂沉默和其他基于 RNA 的沉默系统的理解可能会对生物学所有领域的研究产生广泛的影响。 遗传学、细胞生物学和其他方法将用于识别减数分裂沉默系统所需的机制和机械步骤。更广泛的影响：首席研究员参与了许多教学和指导活动，例如 EXPRESS（理科生接触研究）计划。 为了扩大代表性不足群体的参与，该项目的研究人员将从非博士学位授予机构和少数族裔服务机构招募和培训本科生。 还将实施强调学者准备和指导/教学技能的博士后培训计划。