作为循环系统中的动力来源，心脏的主要功能便是舒缩。然而， 目前我们对调控心肌舒缩功能的生物学机制的了解依然非常有限。我们在前期工作中发现，转录激活反应RNA结合蛋白Trbp，通过促进下游miR-208a的生成并影响心肌中快慢肌纤维伸缩蛋白编码基因的表达，在心肌舒缩功能的调控过程中扮演了关键的角色。我们在进一步的研究中发现，蛋白精氨酸甲基转移酶Prmt5能够与Trbp相互作用，并可以促进Trbp下游miRNA的表达。因此，作为Trbp的互作蛋白，Prmt5可能也参与调控快慢肌基因表达并影响心脏功能。本课题拟通过遗传学手段， 利用生物化学、分子生物学及组学等工具，来探索Trbp与Prmt5的相互作用的在心肌组织中的功能效应以及分子机制。以期能揭示调控心肌发育及功能的新的分子机制，为重建和解析影响心肌舒缩功能的遗传网络，发现心肌舒缩功能障碍的致病因子，以及寻找心肌疾病的治疗策略提供线索。

As the engine underneath the hood of the circulatory system, the primary function of heart is “contraction”. However, our understanding on the regulatory mechanisms underlying cardiac contraction is still very limited. Our previous studies have demonstrated that the Trans-activation response (TAR) RNA-binding protein, Trbp, plays a key role(s) in regulating cardiac contraction, by promoting miR-208a biogenesis and modulating the expression of downstream fast-/slow- twitch myofiber protein-coding genes in cardiomyocytes. In our further investigation, we found that protein Arg methyl-transferase Prmt5 can interact with Trbp, and enhance the expression of its downstream miRNAs. Thus, as a binding partner of Trbp, Prmt5 may participate in regulating the expression of fast-/slow- twitch myofiber genes in cardiomyocytes, and modulating the performance of cardiac muscle. In the proposed study, we will further characterize the interaction between Prmt5 and Trbp, and study the functional consequence(s) and the molecular mechanism(s) in the heart, using genetic, biochemistry, molecular biology and -omics approaches. After completion of the study, we expect to uncover novel regulatory mechanisms underlying cardiac development and function, and contribute to deciphering the genetic networks governing cardiac contraction. Our study could also enable the discovery of new therapeutic targets and lead to new approaches to treatment of cardiac contraction disorders.