RNA结合蛋白Rbm24在人类冠心病发生中转录水平明显上调。申请人此前观察到小鼠及斑马鱼RBM24基因缺失影响心肌正常发育，并发现Rbm24结合翻译起始因子eIF4E，eIF4G，调控蛋白翻译，其结合eIF4E表位中发生Serine181磷酸化。我们推测Rbm24通过控制蛋白翻译影响心肌发育，且其功能由磷酸化介导受引发心肌病环境因子动态调节。本项目拟应用翻译组学研究Rbm24调控蛋白翻译的机制，并鉴定翻译受Rbm24显著调控的关键基因，分析Rbm24翻译调控及候选关键基因对斑马鱼心肌发育的影响。同时将探索引发心肌病环境因子对Serine181磷酸化水平的调节和机制，并分析磷酸化通过动态调节蛋白翻译影响斑马鱼心肌发育的机制。本项目将深入认识Rbm24蛋白翻译调控机制及Serine181对其的动态调节，从而在蛋白翻译水平，并从基因调控与环境因子互作的角度来认识心肌病发生的机制，探寻潜在新靶标。

Human Rbm24 was highly expressed in cases with coronary heart disease versus controls. We found loss of RBM24 gene in mice or zebrafish hampers the normal development of myocardium. We also showed Rbm24 interacts with the translation initiation factor eIF4E, eIF4G and Serine181 phosphorylation occurs within the eIF4E binding site. We suspect Rbm24 dependent translation regulation would affect the development of the myocardium, mediated by Serine181 phosphorylation response to environmental stress causing myocardiopathy. The present study will translatome analyses the mechanisms of Rbm24 dependent translation regulation，to help identify the key translation targets of Rbm24 in myocardium development. Then we will evaluate the effect of Rbm24 dependent translation regulation, as well as the new indentified key genes on the development of the zebrafish myocardium. Moreover, we will examine how environmental stress causing cardiomyopathy alterates the Serine181 phosphrylation of Rbm24, as well as explorer its responsible kinase. Furtherly, we will determine the role of S181 phosphorylation in the development of the zebrafish myocardium through the homeostasis regulation of the Rbm24 dependent translation. The present study will reveal the mechanisms of Rbm24 dependent translation regulation and Serine181 phosphorylation modification, to provide clue for understanding the cause of cardiomyopathy response to environmental factors．