State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Chinese Academy of Sciences, University of Chinese Academy of Sciences, Beijing, China.
FASEB J. 2022 Feb;36(2):e22128. doi: 10.1096/fj.202101279R.
Alternative splicing (AS) is an important mechanism to regulate organogenesis and fertility. Breast carcinoma amplified sequence 2 (BCAS2) is one of the core components of the PRP19 complex, a multiple function complex including splicing, and it is involved in the initiation of meiosis through regulating AS in male mice. However, the role of BCAS2 in mouse oogenesis remains largely unknown. In this study, we found that BCAS2 was highly expressed in the oocytes of primordial follicles. Vasa-Cre-mediated deletion of Bcas2 caused poor oocyte quality, abnormal oogenesis and follicular development. The deletion of Bcas2 in mouse oocytes caused alteration in 991 AS events that corresponded to 706 genes, including Pabpc1l, Nobox, Zfp207, Mybl2, Prc1, and Spc25, which were associated with oogenesis and spindle assembly. Moreover, the disruption of BCAS2 led to degradation of PRP19 core proteins in mouse oocytes. These results suggested that BCAS2 was involved in the AS of functional genes through PRP19 complex during mouse oocyte development.
可变剪接 (AS) 是调节器官发生和生育能力的重要机制。乳腺癌扩增序列 2 (BCAS2) 是 PRP19 复合物的核心组成部分之一，PRP19 复合物是一个多功能复合物，包括剪接，它通过调节雄性小鼠中的 AS 参与减数分裂的起始。然而，BCAS2 在小鼠卵母细胞中的作用在很大程度上尚不清楚。在这项研究中，我们发现在原始卵泡的卵母细胞中高度表达 BCAS2。Vasa-Cre 介导的 Bcas2 缺失导致卵母细胞质量差、异常的卵子发生和卵泡发育。小鼠卵母细胞中 Bcas2 的缺失导致 991 个 AS 事件的改变，这些事件对应 706 个基因，包括 Pabpc1l、Nobox、Zfp207、Mybl2、Prc1 和 Spc25，这些基因与卵子发生和纺锤体组装有关。此外，BCAS2 的破坏导致小鼠卵母细胞中 PRP19 核心蛋白的降解。这些结果表明，BCAS2 通过 PRP19 复合物参与了小鼠卵母细胞发育过程中功能性基因的 AS。
