Role of the SERRATE protein in regulation of miRNA biogenesis and transposable element silencing in Arabidopsis thaliana

这项研究的目标是发现一种名为锯齿(SE)的单一植物蛋白如何在细胞中执行两种截然不同的功能。SE的功能之一是从较大的RNA分子制造小型微型RNA(MiRNAs)，另一功能是抑制基因组中某些潜在有害DNA分子的活动。SE的双功能特性被认为源于它与不同蛋白质伙伴相互作用的能力，这项研究旨在测试这一想法。由于SE在植物和动物中都是保守的，这一结果可能会对许多科学领域和社会产生深远的好处，例如在植物生物技术领域，其结果可能有助于改善农业性状。该项目非常适合本科生参与，并提供遗传学、基因组学和生物化学方面的实践培训。该项目还为研究生和博士后提供了在新兴领域前沿发展他们的职业生涯的机会，因此，该研究将有助于建立一支富有创造力和高技能的劳动力队伍，以支持美国经济的稳定增长。已知Se是植物miRNA加工机械(微处理器)的核心组件。哺乳动物中的SE同源基因是已知的转录因子。初步证据表明，SE与染色质重塑因子的相互作用与其在miRNA加工中的功能有关，而与组蛋白甲基转移酶的相互作用可能介导了其沉默转座子的功能。实验目标将探索这两种功能背后的机制。结果提示SE在miRNA生物发生中的作用可能为更好地调节miRNA的产生和提高依赖小RNA的技术和治疗的有效性和安全性提供新的策略。此外，探索SE在调节转座元件中的新功能将导致将RNA新陈代谢和转录沉默领域结合起来的新发现，并可能为如何克服染色质水平基因沉默的错误调节而导致的动植物疾病提供新的思路。

The goal of this research is to discover how a single plant protein, called SERRATE (SE), carries out two very different functions in the cell. One of SE's functions is to make small microRNAs (miRNAs) from larger RNA molecules, and the other function is to quiet the activity of certain potentially harmful DNA elements in the genome. The bi-functional nature of SE is thought to arise from its ability to interact with different protein partners, and this research aims to test that idea. Because SE is conserved in both plants and animals, the results could have far-reaching benefits for many fields of science and for society, such as in plant biotechnology where the results could contribute to improvement of agricultural traits. This project is well-suited for undergraduate student participation and provides hands-on training in genetics, genomics, and biochemistry. The project also offers opportunities for graduate students and postdoctoral fellows to develop their professional careers at the forefront of an emerging field, and thus the research will contribute to building a creative and highly skilled workforce to support the steady growth of the U.S. economy. SE is known to be a core component of the miRNA processing machinery (microprocessor) in plants. The SE ortholog in mammals is known to function as a transcription factor. Preliminary evidence suggests that interaction of SE with a chromatin-remodeling factor is associated with its function in miRNA processing, whereas interaction with a histone methyltransferase may mediate its function in silencing transposable elements. Experimental aims will explore the mechanisms underlying these two functions. Results that implicate SE activity in miRNA biogenesis could provide new strategies to better regulate miRNA production and to improve the efficacy and safety of technologies and therapies that depend on small RNAs. Moreover, exploring the novel function of SE in regulating transposable elements will lead to new discoveries uniting the fields of RNA metabolism and transcriptional silencing, and may also provide new ideas about how to conquer disorders in plants and animals that result from the mis-regulation of chromatin-level gene silencing.