Transcriptional elongation and mRNA processing occur simultaneously and are highly coupled to increase the efficiency and accuracy of mRNA maturation. Splicing is a step of mRNA processing where intronic regions are removed by spliceosome complexes that bind pre-mRNA. Most human genes with multiple exons are alternatively spliced generating numerous proteins with diverse functions derived from a single gene. Defects in RNA polymerase that alter the transcription elongation rate cause pervasive changes in alternative splicing. Mutations in transcriptional processing cause a variety of human diseases including retina degeneration, which is characterized by photoreceptor cell loss and visual dysfunction that can lead to blindness. Notably, the human retina harbors an astonishing splicing diversity and several retina-specific mRNA isoforms and ubiquitously expressed splicing factors are associated with retinal disease. Retinal photoreceptors, cones and rod cells, constitute over 70% of cells in the retina and initiate the transmission of visual stimuli to the brain by detecting light photons through a molecular pathway known as phototransduction. Many retinal mutations occur in phototransduction genes including rhodopsin, the only photopigment and highest expressed gene in rods. To date, the mechanisms that regulate the precise temporal and quantitative expression of rhodopsin and other phototransduction genes are poorly understood. My preliminary data suggest that the rod-specific transcription factor NRL physically interacts with splicing proteins. I hypothesize that qualitatively and quantitatively precise expression of phototransduction genes are controlled stringently by molecular interactions between the splicing and transcriptional machineries. In this proposal, genetic, biochemical and genomic approaches in combination with high throughput technologies, will be used to identify protein interactions between the transcriptional and splicing machineries. In addition, the role of these interactions will be studied in vitro and in vivo. Furthermore, genomic regions of phototransduction genes associated with RNA polymerase regulation and splicing factor binding will be identified. This grant will expose me to new technologies and computational analysis that will allow me to comprehensively study mechanisms of gene regulation and retinal homeostasis. Overall, this funding opportunity will help me become a well-rounded scientist and achieve research independence in the area of molecular genetics and vision research.