Structure of Dazl based translation control complexes

人类的生育能力依赖于成熟精子和卵子的产生，而在这一过程中基因表达控制的缺陷导致了不孕不育，这一问题影响了全球12%-15%的夫妇。不育男性Y染色体上的缺失提示该位置存在生育因素，随后的作图确定了无精子症(DAZ)基因的缺失。DAZ基因家族的成员是物种在进化过程中生育所必需的。小鼠DAZL是DAZ基因家族的一员，是一种RNA结合蛋白。DAZL在发育中的生殖细胞中识别某些信使RNA上的特定序列，并招募蛋白质辅助因子，以调节该信使RNA产生多少蛋白质，从而决定该基因的表达。我们的目标是确定DAZL蛋白与RNA或蛋白质辅因子结合的三维结构。这将使我们能够可视化这个系统的组件以及它们如何以非常高的分辨率相互作用，展示它们如何正常地控制基因表达。

Human fertility depends upon the production of mature sperm and eggs, and defects in the control of gene expression during this process contribute to infertility, a problem affecting 12-15% of couples worldwide. Deletions on the Y chromosome in infertile men suggested a fertility factor at this location and subsequent mapping identified the Deleted in AZoospermia (DAZ) gene. Members of the DAZ gene family are required for fertility in species across evolution. Mouse Dazl, a member of the DAZ gene family, is an RNA binding protein. Dazl recognises specific sequences on certain messenger RNAs in developing germ cells and recruits protein cofactors in order to regulate how much protein is produced from that mRNA, dictating expression of that gene. We aim to determine the three-dimensional structure of the Dazl protein bound to RNA or the protein cofactors. This will allow us to visualise the components of this system and how they interact at very high resolution, demonstrating how they normally function in controlling gene expression.