Regulation of Gene Expression by a Glycolytic Transcription Factor

基因信息的正确表达对细胞的各项功能至关重要。这个项目解决了一个关于基因表达的基本问题。也就是说，调节基因表达的不同过程是如何协调的，这种协调是如何改变细胞的生物功能的？该项目还将实施有效的方法，扩大代表性不足的学生参与STEM。这些方法利用了从K-12和本科阶段的长期教育和推广努力中获得的技能和经验。从信使rna的合成到它们的广泛加工，基因表达的每一步都是调控的潜在目标。尽管这些调控步骤中的每一个在历史上都被研究为一个生物化学上不同的过程，但近年来，人们已经清楚地认识到它们是高度相互联系和协调的，这种协调是基因调控的基本特征。然而，确定和描述协调这些反应的因素的功能仍然是一项艰巨的挑战。这里描述的研究强调了酵母帽结合复合体（CBC）在基因调控的几乎每一步中意想不到的作用。值得注意的是，其中一种表达受CBC调控的基因GCR1控制着活跃生长细胞中约75%的信使rna的合成。本研究利用GCR1作为工具(1)为转录和RNA加工的协调调控机制以及这种协调对细胞功能的影响提供了一个窗口；(2)了解CBC在基因调控中的功能。该项目有以下独立目标：目标1：确定GCR1是如何被调节的，以及Gcr1p同种异构体是如何允许细胞对营养消耗做出反应的。目的2：确定Cap结合复合物在Gcr1调控中的作用。目的3：利用遗传学和下一代测序方法的结合，确定CBC如何影响染色质修饰和全基因组共转录剪接。

Proper expression of genetic information is crucial to every function performed by cells. This project addresses a fundamental question about gene expression. Namely, how are the different processes that regulate gene expression coordinated and how does this coordination change the biological function of cells? This project will also implement effective approaches for broadening participation of underrepresented students in STEM. These approaches leverage the skills and experiences acquired from a long history of previous education and outreach endeavors at the K-12 and undergraduate levels.Each step in gene expression from the synthesis of messenger RNAs to their extensive processing is a potential target for regulation. Although each of these regulatory steps has been historically studied as a biochemically distinct process, in recent years it has become clear that they are highly interconnected and coordinated, and that this coordination is an essential feature of gene regulation. However, identifying and characterizing the functions of the factors that coordinate these reactions has remained a difficult challenge. The research described here highlights the unexpected role for the yeast cap binding complex (CBC) in nearly every step of gene regulation. Remarkably, one of the genes whose expression is regulated by the CBC, GCR1, controls the synthesis of about 75% of the messenger RNAs in actively growing cells. This proposal leverages GCR1 as a tool to (1) provide a window into mechanisms of coordinated regulation of transcription and RNA processing and the effect of this coordination on cell function and (2) understand CBC functions in gene regulation. The project has the following independent objectives: Objective 1: Determine how GCR1 is regulated and how Gcr1p isoforms allow cells to respond to nutrient depletion. Objective 2: Determine the role of the Cap Binding Complex in Gcr1 regulation. Objective 3: Determine how the CBC affects chromatin modification and co-transcriptional splicing genome-wide using a combination of genetics and next generation sequencing approaches.