The Role of a Novel PIWI-Interacting Protein in Spermatogenesis

描述（由申请人提供）：遗传物质从一代传递到下一代，即从父母传递到子女，是一个关键的生物学过程。然而，这种努力是如何完成的，我们只了解了一部分。我们之前已经发现了一个叫做Piwi蛋白的蛋白质家族，它对这个过程至关重要。为了更详细地了解Piwi是如何工作的，我们已经确定了与它相互作用的其他蛋白质。在果蝇中，Piwi与一种叫做Papi的蛋白质相互作用；这种相互作用是进化保守的，因为小鼠和人类的Piwi和Papi蛋白也会相互作用。在果蝇中，Papi对于胚胎的正常发育和特殊细胞（称为种系细胞）的形成是必需的，这种细胞将遗传信息传递给后代。然而，它在脊椎动物（如老鼠和人类）中的作用尚不清楚。由于Papi对于果蝇胚胎的正常形成及其传递遗传信息的能力是必需的，并且由于它与Piwi蛋白的相互作用是高度保守的，我们假设这种相互作用对哺乳动物Papi蛋白的功能很重要。在这里，我们提出的实验将验证这一假设，并确定小鼠Papi （Mapi）在生殖系调节中的作用。具体来说，我们打算1)研究Mapi在种系发育和成熟性腺中的表达模式，2)确定Mapi在出生后精子发生中的功能，3)表征Mapi蛋白和RNA复合物。

DESCRIPTION (provided by applicant): The passing of genetic material from one generation to the next, i.e. from parents to their children, is a key biological process. How this endeavor is accomplished, however, is only partially understood. We have previously found a family of proteins called the Piwi proteins to be essential for this process. To understand in more detail how Piwi works, we have identified additional proteins which interact with it. In flies, Piwi interacts with a protein called Papi; this interaction is evolutionarily conserved, as Piwi and Papi proteins in mouse and human also interact. In flies, Papi is required for proper development of the embryo and for formation of specialized cells (called germline) which pass genetic information to future generations. However, nothing is known about how it may function in vertebrates such as mice and humans. Because Papi is required for proper formation of fly embryos and their ability to transmit genetic information, and because its interaction with Piwi proteins are highly conserved, we hypothesize that this interaction is important for the function of mammalian Papi proteins. Here, we propose experiments which will test this hypothesis and determine the role of Mouse Papi (Mapi) in regulation of the germline. Specifically, we propose to 1) examine the expression patterns of Mapi during germline development and in mature gonads, 2) determine the function of Mapi during post-natal spermatogenesis, and 3) characterize Mapi protein and RNA complexes. PUBLIC HEALTH RELEVANCE: Sexually reproducing organisms, such as mice and humans, need to pass their genetic information from one generation to the next. This must be accomplished accurately, as mistakes can lead to severe health issues in the offspring, and requires highly specialized tissue in the body to do so. The experiments in this proposal will define how one protein, Mapi, contributes to this process.