BCAS2 is involved in alternative mRNA splicing in spermatogonia and the transition to meiosis.
BCAS2 is involved in alternative mRNA splicing in spermatogonia and the transition to meiosis.
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DOI：
10.1038/ncomms14182
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发表时间：
2017-01-27
影响因子：
16.6
通讯作者：
Li L
中科院分区：
文献类型：
--
作者：
Liu W;Wang F;Xu Q;Shi J;Zhang X;Lu X;Zhao ZA;Gao Z;Ma H;Duan E;Gao F;Gao S;Yi Z;Li L
乳腺癌扩增序列2（BCAS 2）参与多种生物学过程，包括前体mRNA剪接。然而，BCAS 2的生理作用在很大程度上仍然不清楚。在这里，我们报告，BCAS 2是专门富集在小鼠睾丸精原细胞。雄性生殖细胞中Bcas 2的条件性破坏损害精子发生并导致雄性小鼠不育。虽然精原细胞看起来大体正常，但在BCAS 2缺失的睾丸中很少观察到减数分裂前期I和减数分裂事件（重组和突触）中的精母细胞。在BCAS 2缺失的睾丸中，245个基因以选择性剪接形式改变;至少可以验证三个精子发生相关基因（Dazl，Ehmt 2和Hmga 1）。此外，Bcas 2的破坏导致DAZL蛋白的全长形式的显著减少和短形式（缺少外显子8）的增加。总之，我们的研究结果表明，BCAS 2调节精原细胞的选择性剪接和减数分裂起始的过渡，以及男性生育力。乳腺癌扩增序列2（BCAS 2）参与前体mRNA剪接，但其生理作用尚不清楚。在这里，作者发现BCAS 2在小鼠睾丸精原细胞中富集，而BCAS 2在生殖细胞中的缺失改变了精子发生相关基因的选择性剪接，导致男性不育。
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. Breast cancer amplified sequence 2 (BCAS2) is involved in pre-mRNA splicing but its physiological role is unclear. Here, the authors find BCAS2 enriched in mice spermatogonia in the testes, and BCAS2 deletion in germ cells alters alternative splicing of spermatogenesis-related genes, causing male infertility.