RNA结合蛋白及其相变参与生精细胞应激保护的分子机制

生物体常受到的外界刺激包括热刺激、低氧、紫外辐射等经常会激发广泛的翻译抑制以及应激颗粒的形成。应激颗粒是一种由非翻译状态的mRNA与蛋白组装而成的无膜结构，真核细胞受到外界刺激后会迅速调整基因的表达，多聚核糖体从正在翻译的mRNA上解聚从而进入翻译抑制状态。与此同时，许多转录后调控蛋白启动相分离进程，在胞质中浓缩聚集形成特殊的胶状或者淀粉样沉淀构象，在应激状态下保护重要的蛋白与mRNA，有利于细胞存活。.哺乳动物雄性生殖细胞通常在低于体温2-7℃下生存发育，在受到较高温度刺激时会产生应激颗粒，长时间的高温会造成精细胞凋亡增加乃至不育。生殖细胞特异的应激颗粒由哪些成分组成，这些成分如何发挥功能尚不完全清楚。PUM家族和DAZ家族已被发现参与应激颗粒的形成与功能，本项目旨在全面揭示雄性生殖细胞应激颗粒的蛋白和RNA组分，阐明保守的RNA结合蛋白物理构象转变在应激颗粒中的功能机制。

Eukaryotic cells respond to environmental stress such as heat, low oxygen, UV radiation etc. by eliciting a series of subcellular stress response to protect the cells and hence the host organism. One common mechanism is the inhibition of overall protein translation and formation of stress granules, membrane-less organelles containing many RNA binding proteins and RNAs in response to stress. Recent studies have unveiled the components of stress granules in somatic cells and proposed that liquid-liquid phase separation may play important roles in stress granule formation and stress response. However the composition and function of stress granules in animal physiological condition remain largely unknown. We found that several highly conserved RNA binding proteins are key components of stress granules in the testis and multiple pieces of evidence suggest phase change of those protein may be important in protection of spermatogenic cells from stress. We proposed a combined genetic, biochemical and molecular approach to characterize dynamic distribution and composition of stress granules and liquid-liquid phase separation in protecting spermatogenesis against stress.