Regulation, evolution, and function of promoter-associated non-coding RNAs

项目总结/摘要 莱顿核心，博士- 康涅狄格大学= RNA转录的适当调节对于动态控制细胞对环境的反应是必不可少的。 和发展线索。转录调控和RNA生物学领域的教条式转变使我们 为了理解非编码RNA（ncRNA）可以通过多种途径调节蛋白质编码基因的转录， 例如激活剂或阻遏物向基因启动子和增强子的募集或通过影响 RNA加工除了RNA的作用外，转录行为本身也可以积极或消极地 当转录模式重叠时影响启动子活性。这些观察结果表明， ncRNA的生物发生增加了一个复杂的控制层的整体基因表达水平。该提案旨在：（1） 确定调节ncRNA产生和破坏的机制，2）确定ncRNA对局部的影响， 蛋白质编码基因转录和RNA加工，以及3）研究ncRNA的能力， 新基因进化的电容器。理解ncRNA对肿瘤细胞的全面影响的主要障碍是： 基因转录是对非编码转录本的综合鉴定和功能分类的方法 他们这里提出的工作将开发新的实验和计算方法， 转录本的鉴定和预测功能的分类方案。我们将通过实验测试我们的 功能预测，并使用结果为我们的分类系统的进一步修订提供信息。我们将重点 与蛋白质编码启动子重叠或源自蛋白质编码启动子的ncRNA，以确定它们是否受 独立的信号通路以及它们的产生水平是否影响蛋白质的表达- 编码基因最后，使用进化模型来识别与改变的基因相关的核苷酸变化， ncRNA转录物的产生和加工，我们将确定和测试参与ncRNA的机制， 调控以及它们如何在进化过程中作为基因诞生的平台。这些研究将创造 功能转录本注释，这将是那些研究基因表达的主要资源， 上下文此外，我们对ncRNA调控和进化的研究将作为基础工作 以确定这些转录本如何影响发育、疾病和新表型的获得。

PROJECT SUMMARY / ABSTRACT LEIGHTON CORE, Ph.D. – UNIVERSITY OF CONNECTICUT= Proper regulation of RNA transcription is essential for dynamic control of cellular responses to environmental and developmental cues. Dogmatic shifts in the fields of transcription regulation and RNA biology have led us to appreciate that noncoding RNAs (ncRNAs) can regulate transcription of protein-coding genes by diverse mechanisms such as recruitment of activators or repressors to gene promoters and enhancers or by affecting RNA processing. In addition to the role of the RNA, the act of transcription itself can positively or negatively influence promoter activity when transcription patterns overlap. These observations suggest that regulation of ncRNA biogenesis adds an intricate layer of control to overall gene expression levels. This proposal aims to 1) identify the mechanisms that regulate ncRNA production and destruction, 2) determine ncRNA effect on local protein-coding gene transcription and RNA processing, and 3) investigate the ability of ncRNAs to as capacitors for evolution of new genes. The major obstacles in understanding the full impact of ncRNAs on gene transcription is comprehensive identification of non-coding transcripts and methods to functionally classify them. The work proposed here will develop new experimental and computational methods for comprehensive identification of transcripts and a classification scheme that will predict function. We will experimentally test our functional predictions and use the results to inform further revision of our classification system. We will focus on ncRNAs that overlap with or emanate from protein-coding promoters to determine if they are regulated by independent signaling pathways and whether their level of production influences expression from the protein- coding gene. Finally, using an evolutionary model to identify nucleotide changes associated with altered ncRNA transcript production and processing, we will identify and test mechanisms that are involved in ncRNA regulation and how they may serve as a platform for gene birth during evolution. These studies will create functional transcript annotations that will be a primary resource for those studying gene expression in any context. In addition, our investigation of ncRNA regulation and evolution will serve as foundational work towards determining how these transcripts affect development, disease, and acquisition of new phenotypes.