RNA结合蛋白Tulp2在精子发生中的作用及机制研究

RNA binding protein (RBPs) plays a key role in the post-transcriptional control of gene expression. The role of RBPs in spermatogenesis is concerned because of the extensive post transcriptional gene expression control in the process of spermatogenesis. Tulp2 is a new RNA-binding protein identified in our laboratory previously. It is specifically expressed in testis, mainly located in spermatids. Tulp2 knockout male mice are completely sterile, showing abnormal phenotype of oligoasthenoteratozoospermia. Therefore, we speculate that Tulp2 may regulate the expression of the key genes during spermatogenesis at post-transcriptional level, and affect the normal number, morphology and function of sperm. This project intends to combine the knockout mouse model and clinical samples of infertile men, to reveal the biological process that Tulp2 influence sperm count, morphology and vitality; screen the target RNA of Tulp2 and analyze its regulatory mechanism on the gene expression at post transcriptional level; validate teh association of Tulp2 gene with male infertility. Based on the above findings, we will fully clarify the role and mechanism of Tulp2 in spermatogenesis, and provide new cues and effective targets for the etiology, diagnosis and treatment of male infertility.

RNA结合蛋白（RBPs）在基因表达的转录后调控中起着关键作用。由于精子发生过程存在广泛的转录后基因表达控制，所以RBPs在精子发生中的作用受到关注。Tulp2是本实验室前期自主鉴定的一个新的RNA-binding蛋白，它在睾丸特异表达，主要定位于精子细胞；Tulp2基因敲除的雄性小鼠完全不育，呈现少、弱、畸精子的异常表型。由此我们推测：Tulp2可能在转录后水平发挥其对精子发生关键基因的调控作用，从而影响正常数量、形态和功能精子的形成。本项目拟结合敲除小鼠模型和临床不育人群样本，深入揭示Tulp2影响精子数量、形态和活力的生物学过程；同时筛选Tulp2在发挥功能时的靶标RNA，分析其在转录后水平调控基因表达的机制；进一步验证该基因在不育人群的关联性。综上研究结果，全面阐明Tulp2在精子发生中的作用和机制，为临床男性不育的病因解析及诊断治疗提供新的思路和有效靶标。