非梗阻无精症是一类常见的男性不育症，对其致病机制了解得不多。我们前期工作表明，剪接体外围组分U2A特异调控果蝇精原细胞的分化，差异作用于精原细胞mRNA的剪接，并且是人类非梗阻无精症的易感基因(PNAS 2016)。然而U2A作为剪接体的一个外围固定组分，如何差异地作用于精原细胞中特定的剪接信号，影响特定类型基因的剪接，其具体的分子机制仍然未知。因此，本项目将开展以下研究：1)阐明U2A差异作用于精原细胞mRNA剪接的序列识别特点和相关信息；2)鉴定U2A差异作用于精原细胞mRNA剪接的反式调控因子DSP1等；3)明确DSP1等调控U2A差异作用于精原细胞mRNA剪接的分子机制。本项目将提高我们对精原细胞中剪接体识别和调控机制的认识，深入揭示临床非梗阻无精症与剪接体差异调控mRNA剪接的相关性，并为临床非梗阻无精症的诊断和治疗提供线索。

Nonobstructive azoospermia (NOA), a common but poorly understood cause of male infertility in humans. Our previous works showed that spermatogonia lacking a spliceosome factor U2A specifically fail to undergo the spermatogonia differentiation and proper splicing for some mRNA, leading to disruption of spermatogenes resulting in Non-obstructive azoospermia (NOA). However, the molecular mechanism of how U2A differentially acts on mRNA splicing and expression in spermatogonia remains largely unknown. Thus, it is very necessary to perform this project with the following aims. 1) To characterize the cis information recognized differentially by U2A in spermatogonia. 2) To uncover the interacting protein DSP1 to regulate U2A differentially acting on mRNA splicing. 3) To determine the molecular mechanism about U2A differentially acts on mRNA splicing in spermatogonia. This project will not only provide us insights into the mechanisms about specific gene splicing in germ cells, but also promote us understanding the development of spermatogonia. Importantly, it could offer valuable information for prevention and treatment of NOA in humans.