CAREER: The Mechanism and Genome-Wide Regulation of Genes and Transposable Elements by Epigenetically Active Small Interfering RNAs

职业：表观遗传活性小干扰 RNA 对基因和转座元件的机制和全基因组调控

• 批准号: 1252370
• 负责人: R Keith Slotkin
• 金额: $ 81.68万
• 依托单位: Ohio State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1252370&HistoricalAwards=false
• 关键词: CAREER; Mechanism; Genome; Wide; Regulation

Intellectual Merit. Transposable elements (TEs) are mobile and can insert into genes, causing mutations. To guard against this mutagenic potential, organisms have evolved mechanisms to repress transcription of TEs. Recently the PI's laboratory has discovered that when TEs are transcriptionally activated in Arabidopsis plants, many of the TE transcripts are processed into large quantities of novel small RNAs that are termed epigenetically active small interfering RNAs (easiRNAs). These easiRNAs are hypothesized to be responsible for the initiation of silencing of active TEs, the establishment of epigenetic regulation in the form of DNA methylation, as well as production of large-scale transcriptomic changes. The major goal of this project is to explore how easiRNA biogenesis is triggered and to understand the multiple biological functions of easiRNA production. Investigation of these processes is critical for understanding how the genome maintains integrity and survives TE transcriptional activation, as well as how a cell can recognize what needs to be expressed (cellular genes) from what should be silenced (TEs). Moreover, easiRNA influence on multiple cellular functions may explain some important agricultural phenomena, and therefore it is fundamental to understand these mechanisms and which genes are affected.Broader Impacts. This project will support training and mentoring of undergraduate, graduate and post-doctoral scientists. In addition, the project will include two independent activities designed to best integrate the PI's research, teaching, and diversity outreach components. First, the PI's current Young Scholars Program Biology Enhancement Workshop, which is taught to 7th grade students from the urban Columbus public school system, will be continued and leveraged to generate the Young Scholars Program Biology Internships. In this novel program middle school underrepresented minorities in STEM disciplines will be integrated into the PI?s laboratory and get real biology laboratory experience and advance biological discovery while engaged in training and learning exercises. Once the internship is completed, the student will automatically transition into a scientific mentoring program with the PI. This program will be expanded to include other PIs and will impact the community by providing a professional scientific research experience with extended mentoring to underrepresented students. Second, the PI will fully integrate the research in this project into an annual upper-division undergraduate laboratory course. With help from Course Design Institute of the Ohio State University Center for the Advancement of Teaching, the PI will integrate specific sub-aims from this project into the undergraduate laboratory curriculum and education. The original data produced from the course experiments will be published by the class in an undergraduate research journal and will be used directly by the PI. This course will leverage the Department of Molecular Genetics teaching infrastructure to teach and train undergraduate students molecular biology, while also exciting students about advancing scientific discovery.

智力优势。 转座因子是移动的，可以插入基因，引起突变。 为了防止这种潜在的致突变性，生物体已经进化出抑制TE转录的机制。最近，PI的实验室发现，当TE在拟南芥植物中被转录激活时，许多TE转录本被加工成大量的新的小RNA，这些小RNA被称为表观遗传活性小干扰RNA（epigenetically active small interfering RNA，ESTRNA）。这些mRNA被假设负责启动活性TE的沉默，以DNA甲基化的形式建立表观遗传调控，以及产生大规模转录组学变化。该项目的主要目标是探索如何触发BCRRNA生物合成，并了解BCRRNA生产的多种生物学功能。研究这些过程对于理解基因组如何保持完整性并在TE转录激活中存活，以及细胞如何识别需要表达的（细胞基因）和应该沉默的（TE）至关重要。此外，mRNA对多种细胞功能的影响可以解释一些重要的农业现象，因此了解这些机制以及哪些基因受到影响是至关重要的。 该项目将支持对本科生、研究生和博士后科学家的培训和指导。 此外，该项目将包括两个独立的活动，旨在最好地整合PI的研究，教学和多样性外展组成部分。首先，PI目前的青年学者计划生物学增强研讨会，这是教7年级学生从城市哥伦布公立学校系统，将继续和杠杆产生青年学者计划生物学实习。在这个新的计划中学在STEM学科代表性不足的少数民族将被纳入PI？的实验室和获得真实的生物实验室的经验和推进生物发现，同时从事培训和学习练习。一旦实习完成，学生将自动过渡到PI的科学指导计划。该计划将扩大到包括其他PI，并将通过为代表性不足的学生提供专业的科学研究经验来影响社区。 第二，PI将把本项目的研究完全整合到每年的高年级本科实验室课程中。在俄亥俄州州立大学教学促进中心课程设计研究所的帮助下，PI将把本项目的具体子目标整合到本科实验室课程和教育中。课程实验所得的原始数据将由班级发表在本科研究期刊上，并直接供PI使用。本课程将利用分子遗传学系的教学基础设施来教授和培训本科生分子生物学，同时也让学生对推进科学发现感到兴奋。