RHAU是一种RNA结合蛋白，具有解旋酶活性。在小鼠中剔除Rhau导致胚胎死于第7.5天（E7.5), 中胚层不能形成,提示RHAU在心脏中胚层形成和早期心脏发育过程中起重要作用。我们在心脏中胚层中将RHAU剔除，发现心脏发育出现缺陷，胚胎死于E11.5天左右。Nkx2-5是心脏中胚层形成之后最早表达的转录因子，我们发现Rhau剔除后影响Nkx2-5 mRNA的稳定性及翻译，导致Nkx2-5蛋白水平下降，可能是导致心脏发育缺陷的部分原因。在本申请中，我们拟深入研究RHAU协调调控Nkx2-5 mRNA翻译和稳定性的先后顺序，以及寻找新的受RHAU调控的参与心脏发育的mRNA分子。该研究将增加我们对mRNA非翻译序列调控作用的认识，帮助理解心脏发育的调控机制，为心脏发育缺陷的预防和干预提供理论基础。

RHAU is one of the RNA binding proteins with helicase activity. Deletion of Rhau in mice causes embryonic lethality at E7.5 and results in gastrulation defects, suggesting of important role of RHUA in cardiac mesoderm formation and early heart development. We deleted Rhau in cardiac mesoderm and found cardiac malformation leading to embryonic lethality at around E11.5. Nkx2-5 is the earliest to express in cardiac crescent after cardiac mesoderm formation. We found that Rhau deletion had an impact on Nkx2-5 mRNA stability and translation leading to reduced Nkx2-5 protein levels, which may be one of the reasons for heart defects. In this application, we plan to investigate the following issues: 1. Coordinated regulation of Nkx2-5 mRNA stability and translation by RHAU; 2. Search for new mRNA targets of RHAU that are involved in heart development. This study will increase our understanding the function of mRNA untranslational regions (UTRs) and help elucidate the regulatory mechanisms on heart development, which in turn will provide theoretical foundation for prevention and intervention against heart defects in the future.