Genetic and molecular dissection of meiotic silencing and unpaired DNA detection.

减数分裂沉默和未配对 DNA 检测的遗传和分子解剖。

• 批准号: 7539381
• 负责人: Thomas Michael Hammond
• 金额: $ 4.68万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-16 至 2011-05-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7539381
• 关键词: Alleles; Animals; Area; Be++ element; Beryllium; Biochemistry; Biological Process; Cells; Cloning; Collection; DNA; DNA Sequence Rearrangement; Defense Mechanisms; Detection; Dissection; Double-Stranded RNA; Elements; Eukaryota; Eukaryotic Cell; Event; Evolution; Figs - dietary; Future; Gene Mutation; Gene Silencing; Generations; Generic Drugs; Genes; Genetic; Genetic Recombination; Genetic Transcription; Genome; Genome Scan; Goals; Hereditary Disease; Human; Human Genome; Knock-out; Knowledge; Length; Link; Localized; Maps; Mediating; Meiosis; Modeling; Molecular; Molecular Biology; Molecular Genetics; Mutation; Nature; Neurospora; Neurospora crassa; Organism; Pattern; Prevention; Process; Proteins; RNA; RNA Interference; RNA-Directed RNA Polymerase; Reproduction spores; Research; Resistance; Role; Screening procedure; Small RNA; Transcript; Virus; Work; base; biological research; fungus; genetic element; high throughput screening; human DICER1 protein; mutant; protein protein interaction; research study; transmission process

DESCRIPTION (provided by applicant): Meiotic silencing is a phenomenon observed in animals and fungi whereby unpaired genes or other genetic elements are turned off during meiosis. The fact that it is triggered by unpaired DNA makes it ideally suited for the control of selfish genetic elements, such as viruses and transposons. Although meiotic silencing appears to be a type of RNA silencing - a generic term referring to small RNA mediated processes in eukaryotes - little else is known about its mechanistic nature. This proposal's primary goal is to investigate the unknown aspects of meiotic silencing, particularly the unpaired DMA detection process, using the eukaryotic organism in which it was initially discovered: Neurospora crassa. Specific aims to reach this goal include: 1) to develop and implement a high-throughput screen to identify meiotic silencing mutants 2) to identify and characterize the aberrant RNA transcripts theorized to be transcribed from unpaired meiotic DNA and 3) to clone and characterize alleles conferring resistance to [meiotic silencing-suppressing] meiotic drive elements. Relevance: Human selfish genetic elements have been linked to several genetic diseases. The research proposed herein seeks to elucidate the mechanism of meiotic silencing, a recently discovered biological process that may help defend the human genome from selfish genetic elements. Knowledge gained from this study could benefit future efforts towards the prevention of genetic disorders.

描述（由申请人提供）：减数分裂沉默是在动物和真菌中观察到的一种现象，其中未配对的基因或其他遗传元件在减数分裂期间被关闭。它是由未配对的DNA触发的，这一事实使它非常适合控制自私的遗传元件，如病毒和转座子。虽然减数分裂沉默似乎是RNA沉默的一种类型-一个通用术语，指的是真核生物中的小RNA介导的过程-很少有人知道它的机制性质。该提案的主要目标是研究减数分裂沉默的未知方面，特别是未配对的DNA检测过程，使用最初发现它的真核生物：粗糙脉孢菌。实现这一目标的具体目标包括：1）开发和实施高通量筛选以鉴定减数分裂沉默突变体; 2）鉴定和表征理论上由未配对减数分裂DNA转录的异常RNA转录物; 3）克隆和表征赋予对[减数分裂沉默抑制]减数分裂驱动元件抗性的等位基因。相关性：人类自私的遗传因素与几种遗传疾病有关。本文提出的研究旨在阐明减数分裂沉默的机制，这是一种最近发现的生物学过程，可能有助于保护人类基因组免受自私遗传因素的影响。从这项研究中获得的知识可能有助于未来预防遗传性疾病的努力。