International Peace Maternity and Child Health Hospital, Shanghai Key Laboratory for Reproductive Medicine, School of Medicine, Shanghai Jiaotong University, 200030 Shanghai, China.
Institute of Reproductive Medicine, School of Medicine, Nantong University, 226021 Nantong, Jiangsu, China.
Biol Reprod. 2019 Feb 1;100(2):561-572. doi: 10.1093/biolre/ioy213.
The expression of many genes during the postmeiotic stages of spermatogenesis is largely regulated by germ cell-specific RNA-binding proteins at the level of posttranscription. One of these RNA-binding proteins, YBX2, participates in mRNA storage and regulation of translation in haploid spermatids. How YBX2-stored mRNAs become translationally competent during spermiogenesis remains unknown. In the present study, we report for the first time that YBX2 interacts with PAIP1, a protein translation enhancer, in vitro and in vivo. In murine testes, PAIP1 is highly expressed and colocalizes with YBX2 in round spermatids. Using sequential RNA immunoprecipitation and sequence analysis, we identified a group of spermiogenic mRNAs indirectly bound by PAIP1 through YBX2. Translation of mRNAs bearing the YBX2 target sequence was significantly blocked by YBX2 protein, but was reinitiated when YBX2 was coexpressed with PAIP1 in vitro. Taken together, these results indicate that PAIP1 regulates the translation of YBX2-masked mRNAs during spermiogenesis, and we propose this YBX2-PAIP1 interaction plays an important role in male germ cell development.
在精子发生的减数分裂后阶段，许多基因的表达在很大程度上受到转录后水平上的生殖细胞特异性 RNA 结合蛋白的调节。这些 RNA 结合蛋白之一，YBX2，参与了单倍体精细胞中 mRNA 的储存和翻译调控。在精子发生过程中，YBX2 储存的 mRNA 如何变得具有翻译能力仍然未知。在本研究中，我们首次报道 YBX2 在体外和体内与 PAIP1（一种蛋白质翻译增强子）相互作用。在小鼠睾丸中，PAIP1 高度表达，并与 YBX2 在圆形精细胞中共定位。通过连续的 RNA 免疫沉淀和序列分析，我们鉴定了一组通过 YBX2 间接结合的精子发生 mRNA。含有 YBX2 靶序列的 mRNA 的翻译被 YBX2 蛋白显著阻断，但当 YBX2 与 PAIP1 在体外共表达时，翻译被重新启动。综上所述，这些结果表明 PAIP1 在精子发生过程中调节 YBX2 掩蔽的 mRNA 的翻译，我们提出 YBX2-PAIP1 相互作用在雄性生殖细胞发育中发挥重要作用。
