EAGER: Coupling of Transcription and mRNA Decay in Mammalian Cells

智力优势：“DNA为mRNA编码，为蛋白质编码”是细胞中基因表达的成熟模型。 然而，最近的证据表明，我们细胞中基因表达的调控有许多额外的细微差别，这些细微差别是这个简单模型所没有预料到的。 已知细胞质中mRNA的量是mRNA的产生速率（转录）以及mRNA的降解速率两者的产物。 该研究项目的基本假设是，有一种方式可以将细胞质mRNA的状态传递回细胞核并影响转录速率。 换句话说，如果细胞质中特定mRNA的降解速率增加，则可以将信号发送回细胞核以增加合成（转录）速率，从而维持细胞质中mRNA的稳态水平。 已经获得的初步证据表明，这很可能是这种情况下，本研究项目的目标是正式测试这一假设的概念证明研究。 mRNA将信号发送回细胞核以调节自身合成的能力是一个新的想法，它对细胞中遗传信息的表达方式具有根本性的影响。 因此，充分理解这一过程在各种生物学科中具有重要意义。 更广泛的影响：该研究项目汇集了一个跨学科的团队，将导致研究生和博士后水平的研究人员的交叉培训。 这种跨学科培训将为这些学员提供未来职业成功的重要技能。 该项目将努力招募代表性不足的人群参与研究工作，以增强科学多样性。 该项目的数据将被纳入高级本科/研究生课程，让广泛的学生接触尖端研究。 推广活动包括在互联网网站上发布信息和在科学博览会上与高中生会面，将提高公众的科学素养。 最后，所开发的数据、技术和模型将存放在易于访问的数据库中，并广泛传播，以促进跨学科纳入该项目的潜在变革思想。

Intellectual Merit: 'DNA codes for mRNA codes for Protein' is the well-established model of gene expression in cells. Recent evidence, however, suggests that the regulation of gene expression in our cells has many additional nuances that were not anticipated by this simple model. The amount of mRNA in the cytoplasm is known to be a product of both the rate of production of the mRNA (transcription) as well as the degradation rate of the mRNA. The underlying hypothesis for this research project is that there is a way for the status of the cytoplasmic mRNA to be communicated back to the nucleus and influence the rate of transcription. In other words, if the rate of degradation of a specific mRNA in the cytoplasm is increased, a signal can be sent back to the nucleus to increase the rate of synthesis (transcription), thus maintaining a steady-state level of the mRNA in the cytoplasm. Preliminary evidence has been obtained to suggest that this may well be the case and the goal of this research project is to formally test this hypothesis in proof of concept studies. The ability of an mRNA to send signals back to the nucleus to regulate its own synthesis is a novel idea that has fundamental bearing on how genetic information in cells is expressed. Thus a full understanding of this process has important implications in a variety of biological disciplines. Broader Impacts: The research project brings together an interdisciplinary team that will result in the cross-training of both graduate students and postdoctoral level researchers. Such interdisciplinary training will provide an important skillset to these trainees for future career success. The project will strive to recruit underrepresented populations into the research endeavors to enhance scientific diversity. Data from the project will be incorporated into an advanced undergraduate/graduate course to give a broad set of students exposure to cutting-edge research. Outreach activities including posting on internet sites and meeting with high school students at science fairs, will raise public scientific literacy. Finally, the data, technology and models that are developed will be deposited in easily accessible databases and disseminated widely to promote the interdisciplinary incorporation of the potentially transformative ideas of the project.