Photoreceptor neuron specific alternative splicing messenger RNA

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Project Summary The project will characterise a new genetic model of retinal degeneration that can potentially shed light on the mechanisms of age-related vision loss in humans (Aim 1). We will also investigate how two RNA binding proteins, Musashi 1 and 2 (MSI1, MSI2), regulate synthesis of proteins in the photoreceptor cells. We have shown that MSI1 and MSI2 are required for the development, function and survival of photoreceptor cells. However, the exact role of the two proteins in photoreceptor cells and the reasons why they are needed remain unclear. We propose that the main role of the Musashi proteins in photoreceptors is to promote the expression of proteins involved in light perception. The processes supported by Musashi include the phototransduction cascade that converts light into electrical signals and the transmission of these signals to a chain of neurons leading to the brain. This hypothesis is supported by substantial preliminary data on the targets and interactions of the Musashi proteins, and the visual function of mice in which the two genes are disabled. In Aim 2 of the project we will use three genes involved in vision that we identified in our preliminary work as Musashi targets to determine how Musashi controls the amount of protein they produce. In Aim 3 of the project we will determine which proteins in the retina are directly regulated by Musashi. This data will give us a global view of how Musashi controls protein production and which structures and processes in the photoreceptor cells are shaped by Musashi. Taken together the data gathered by the research proposed under the three aims will allow us to paint a detailed picture of the Musashi protein function that connects interactions between individual molecules to the function of the eye and its ability to perceive the world around us. We expect that our work will open the road to new therapeutic approaches for treating blindness that will boost protein production to compensate for reduction in function caused by genetic mutations.