Photoreceptor neuron specific alternative splicing messenger RNA

项目摘要 该项目将描述一种新的视网膜变性遗传模型，这种模型可能会脱落 人类与年龄相关的视力丧失的机制(目标1)。我们还将调查两个RNA是如何 结合蛋白Musashi 1和Musashi 2(MSI1，MSI2)调节光感受器细胞蛋白质的合成。我们 已经证明MSI1和MSI2是光感受器的发育、功能和生存所必需的 细胞。然而，这两种蛋白质在光感受器细胞中的确切作用以及需要它们的原因 目前仍不清楚。我们认为武藏蛋白在光感受器中的主要作用是促进 参与光感知的蛋白质的表达。武藏支持的流程包括 将光转换成电信号的光传导级联，这些信号的传输到 通向大脑的神经元链。这一假设得到了大量初步数据的支持 武藏蛋白的靶点和相互作用，以及这两个基因所在小鼠的视觉功能 已禁用。 在项目的目标2中，我们将使用我们在初步研究中确定的与视觉有关的三个基因 作为武藏的目标，确定武藏如何控制他们生产的蛋白质的数量。 在该项目的目标3中，我们将确定视网膜中哪些蛋白质受到武藏的直接调控。 这些数据将让我们对武藏如何控制蛋白质生产以及哪些结构和 光感受器细胞的突起是由武藏塑造的。 综合起来，在这三个目标下提出的研究收集的数据将使我们能够描绘 武藏蛋白功能的详细图片，连接单个分子之间的相互作用 眼睛的功能及其感知周围世界的能力。我们期待着我们的工作将开启 通往治疗失明的新治疗方法之路，这将促进蛋白质生产以补偿 用于基因突变导致的功能减退。

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.