School of Life Sciences, University of Science and Technology of China, Hefei 230026, China.
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Nat Commun. 2017 Jan 27;8:14182. doi: 10.1038/ncomms14182.
Breast cancer amplified sequence 2 (BCAS2) is involved in multiple biological processes, including pre-mRNA splicing. However, the physiological roles of BCAS2 are still largely unclear. Here we report that BCAS2 is specifically enriched in spermatogonia of mouse testes. Conditional disruption of Bcas2 in male germ cells impairs spermatogenesis and leads to male mouse infertility. Although the spermatogonia appear grossly normal, spermatocytes in meiosis prophase I and meiosis events (recombination and synapsis) are rarely observed in the BCAS2-depleted testis. In BCAS2 null testis, 245 genes are altered in alternative splicing forms; at least three spermatogenesis-related genes (Dazl, Ehmt2 and Hmga1) can be verified. In addition, disruption of Bcas2 results in a significant decrease of the full-length form and an increase of the short form (lacking exon 8) of DAZL protein. Altogether, our results suggest that BCAS2 regulates alternative splicing in spermatogonia and the transition to meiosis initiation, and male fertility.
乳腺癌扩增序列 2（BCAS2）参与多种生物学过程，包括前体 mRNA 的剪接。然而，BCAS2 的生理作用在很大程度上仍不清楚。在这里，我们报告 BCAS2 特异性富集在小鼠睾丸精原细胞中。在雄性生殖细胞中条件性敲除 Bcas2 会损害精子发生，导致雄性小鼠不育。尽管精原细胞看起来大体正常，但在 BCAS2 耗尽的睾丸中很少观察到减数分裂前期 I 的减数分裂和减数分裂事件（重组和联会）。在 BCAS2 缺失的睾丸中，有 245 个基因发生了可变剪接形式的改变；至少有三个与精子发生相关的基因（Dazl、Ehmt2 和 Hmga1）可以被验证。此外，破坏 Bcas2 会导致 DAZL 蛋白全长形式的显著减少和短形式（缺少外显子 8）的增加。总之，我们的结果表明，BCAS2 调节精原细胞中的可变剪接和向减数分裂起始的转变，以及男性生育能力。
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