Functional Analysis of microRNAs in C. elegans spermatogenesis

7.项目总结 小RNAs，包括microRNAs，已经被证明在调节 基因在生殖系中的表达。然而，具体的路径和目标是由个人调节的 精子发生过程中的microRNAs在很大程度上仍不清楚。直接性的认定 由单个microRNAs调控的靶标仍然是该领域的一个核心挑战。在这笔赠款中，我们 建议确定生殖系microRNAs的直接靶点，这些微RNA在调节 精子发生。我们正在使用线虫的模型系统，它在定义 个体microRNA调控发育途径靶标的核心原则。在之前 在这项工作中，我们和其他人已经确定了在线虫生殖细胞和 体细胞性腺细胞。此外，我们还发现了一组能够调节精子的微RNA 队形。然而，他们监管的途径和目标在很大程度上仍未确定。这 这项工作将解决两个核心问题：1)与生殖系相关的靶基因是什么 特定的ArgAerte蛋白？2)microRNAs如何通过靶mRNAs的3‘UTR进行调节 采取行动控制精子生成？这项工作将为今后的调查提供基础 全面定义在胚系中作用的microRNA靶点，以调节 精子发生。

7. PROJECT SUMMARY Small RNAs, including microRNAs, have been shown to play critical roles in the regulation of gene expression in the germ line. However, the specific pathways and targets regulated by individual microRNAs in the process of spermatogenesis remain largely unknown. The identification of direct targets regulated by individual microRNAs remains a central challenge in the field. In this grant, we propose to identify direct targets of germline microRNAs that function in the regulation of spermatogenesis. We are using the model system of C. elegans, which has been instrumental in defining the core principles of individual microRNA regulation of targets in developmental pathways. In prior work, we and others have identified the set of microRNAs that are expressed in C. elegans germ cells and somatic gonad cells. Additionally, we have identified a set of microRNAs that function to regulate sperm formation. However, the pathways and targets that they regulate remain largely uncharacterized. This work will address two central questions: 1) What are the target mRNAs that associate with a germline specific Argonaute protein? 2) How does regulation by microRNAs through the 3’ UTR of target mRNAs act to control spermatogenesis? This work will provide a foundation for future investigation to comprehensively define the microRNA targets that act in the germ line to regulate the process of spermatogenesis.