Regulation of Gene Expression by the Yeast Cap Binding Complex: Coordinating Transcription and RNA Processing

点击翻译按钮获取中文摘要

Intellectual Merit. Proper expression of genetic information is crucial to every function performed by the cell. One of the first steps in gene expression is the synthesis of a messenger RNA molecule from its DNA template. This messenger RNA (mRNA) must be extensively processed in order for this molecule to be exported from the cell nucleus and translated to make the proteins that sustain the functions of the cell. As part of its "processing" the RNA must be modified at both of its ends to ensure its stability and export. Furthermore, noncoding sequences that interrupt the protein-coding sequence of the RNA must be removed through the process of mRNA splicing. Each step in gene expression--from the synthesis of messenger RNAs to their extensive processing--is a potential target of regulation. Although each of these regulatory steps has been historically studied as a biochemically distinct reaction, in recent years it has become clear that these processes 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), a protein complex that binds to the 5' end of the mRNA and has well-characterized roles in RNA splicing and RNA processing, in tight control of RNA synthesis. This work explores the extensive network of interactions that are orchestrated by the cap binding complex and elucidates the mechanisms by which the CBC acts to regulate RNA synthesis and coordinate RNA synthesis with the various other steps of gene expression.Broader Impacts. Educational activities associated with this project focus on directed approaches to increase access and opportunities for students from groups traditionally underrepresented in the sciences. Using skills and experiences acquired from a broad repertoire of previous education and outreach endeavors, this educational plan has two main goals. First, strategies will be developed for sustained engagement with local high schools with high populations of underrepresented minority students. These specific outreach activities expose students to mentored research opportunities and assist teachers in developing curricula that integrate the high school curriculum with cutting-edge gene expression research. Furthermore, they establish mechanisms to facilitate these students' transitions to undergraduate studies and, ultimately, to careers in the biological sciences. The second goal is to develop research opportunities for minority undergraduates at University of California-San Diego that will broaden participation of these underrepresented groups in the sciences.