卵细胞成熟是一个复杂的生理过程，包括细胞核成熟和细胞质成熟，并通过两次减数分裂过程完成。苏有强等发现Marf1（meiosis arrest female 1）基因突变表现为卵细胞减数分裂停滞和雌性不育的表型，但其调控的分子机制还不清楚。本项目将围绕MARF1的结构和机制开展以下三方面研究：（1）通过X射线晶体学解析MARF1蛋白含有的结构域（NYN，RRM和LOTUS结构域）或者片段的晶体结构；（2）通过生化实验研究MARF1结合和降解RNA底物的活性，获得MARF1底物特异性结合的核酸序列；（3）结合X射线晶体学和冷冻电镜技术研究全长MARF1蛋白及其结合RNA底物复合物的结构，揭示其识别底物并降解的分子机制。本项目的目标是首次阐明MARF1的结构以及作用底物的分子机制，将为深入研究MARF1对卵细胞成熟的调控机制打下基础，对防治女性不孕不育以及研制新型更有效的女性避孕药具有重要意义。

The abnormality of oogenic process is one of the major reasons of female infertility. Oogenic process is essential for producing fertilization-competent oocyte, including accurate completion of two-step meiosis, cytoplasmic maturation and maintenance of genomic integrity. Su et al. found that MARF1 (meiosis arrest female 1) is required for these process and mutation of Marf1 cause meiotic arrest and female infertility. Further study demonstrated that MARF1 regulates cytoplasmic maturation and retrotransposon silencing by suppressing levels of specific transcripts. However, its underlying molecular mechanism is unknown. This projects will focus on three aspects of structure and molecular mechanism of MARF1: (1) elucidating the crystal structures of the novel domains (NYN, RRM and LOTUS domains) and fragments of MARF1 using X-ray crystallography; (2) assessing the RNA binding and nuclease activity of MARF1 by the biochemical study, and obtaining the specific RNA binding motif by an in vitro selection method combined SELEX (Systematic Evolution of Ligands by exponential enrichment) and NGS (Next-generation sequencing); (3) studying the structures of full-length MARF1 protein and its complex with substrates by a combination of X-ray crystallography and Cryo-EM techniques, and revealing the molecular mechanism of substrate recognition and degradation. The aim of this project is to illuminate the molecular structure of MARF1 and its recognition of substrates, and to provide basis for further study of regulation mechanism of MARF1 for oogenic process, which will be of significance for prevention and treatment of female infertility and development of more effective medicine for birth control.