Regulation of Non-Canonical Telomerase RNA

这项研究将研究一种新的基于RNA的机制，该机制允许植物对影响DNA的胁迫做出反应，并传递保护染色体完整性的信号，这对植物生育力，生长和疾病预防至关重要。该项目将开发对培育和种植更健康的植物有价值的基础知识。 该项目将把基础植物科学研究与下一代植物科学家的教学和培训结合起来。 作为这一努力的一部分，实验室管理研讨会的博士后研究员和新的教师将进行，并将在这个主题上的研究生课程开发。这个项目的总体目标是阐明TER 2，一种新的端粒相关的长非编码RNA（lncRNA）的分子机制和调控从模式植物拟南芥。TER 2是端粒酶的负调节因子，其响应于DNA双链断裂而迅速稳定。TER 2的诱导抑制端粒酶活性，并被假设为促进DNA损伤的忠实修复。TER 2通过一种未知的机制对生殖健康也是必要的。生物化学，遗传学，细胞生物学和计算策略的组合将用于研究TER 2。 目标1将定义调节TER 2加工/代谢的关键结构元件，以鉴定TER 2内的DNA损伤传感器和控制TER 2稳定性的元件。 目的2将通过测试TER 2是否是Dicer 2切割的底物来研究小RNA加工机制在促进TER 2周转中的作用。目的3将通过测试ter 2突变体中与育性相关的缺陷是否反映了异常的雄性配子发生或父系表达的印迹基因的影响来研究TER 2在拟南芥生殖中的贡献。 总之，这项工作的结果将建立lncRNA调控的新范式，并增加对促进基因组稳定性的基于RNA的途径的理解。

This study will investigate a novel RNA-based mechanism that allows plants to respond to stress that affects the DNA, and to transmit a signal that protects chromosome integrity, which is important for plant fertility, growth and disease prevention. This project will develop fundamental knowledge valuable for breeding and growing healthier plants. This project will integrate basic plant science research with the teaching and training of the next-generation of plant scientists. As part of this effort, laboratory management workshops for postdoctoral fellows and new faculty will be conducted, and a graduate course on this topic will be developed.The overarching goal of this project is to elucidate the molecular mechanism and regulation of TER2, a novel telomerase-associated long noncoding RNA (lncRNA) from the model plant Arabidopsis thaliana. TER2 is a negative regulator of telomerase that is rapidly stabilized in response to DNA double-strand breaks. Induction of TER2 represses telomerase activity and is hypothesized to promote faithful repair of DNA damage. TER2 is also necessary for reproductive fitness through an unknown mechanism. A combination of biochemical, genetic, cell biological and computational strategies will be used to study TER2. Objective 1 will define key structural elements that regulate TER2 processing/metabolism for the purpose of identifying the DNA damage sensor within TER2 and the elements that control TER2 stability. Objective 2 will investigate the role of small RNA processing machinery in promoting TER2 turnover by testing if TER2 is a substrate for cleavage by Dicer 2. Objective 3 will examine the contribution of TER2 in Arabidopsis reproduction by testing whether the fertility-related defects in ter2 mutants reflect aberrant male gametogenesis or the effect of a paternally expressed imprinted gene. Altogether, the results of this work will establish new paradigms for lncRNA regulation and increase understanding of RNA-based pathways that promote genome stability.