Regulation of Gene Expression by a Glycolytic Transcription Factor

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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.