Li Haixin, Liang Zhuqing, Yang Jian, Wang Dan, Wang Hanben, Zhu Mengyi, Geng Baobao, Xu Eugene Yujun
State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 211166, China.
Natl Sci Rev. 2019 May;6(3):455-468. doi: 10.1093/nsr/nwy163. Epub 2018 Dec 28.
Expression of () is a hallmark of vertebrate germ cells, and is essential for embryonic germ cell development and differentiation, yet the gametogenic function of has not been fully characterized and most of its direct targets remain unknown. We showed that postnatal stage-specific deletion of in mouse germ cells did not affect female fertility, but caused complete male sterility with gradual loss of spermatogonial stem cells, meiotic arrest and spermatid arrest. Using the genome-wide high-throughput sequencing of RNAs isolated by cross-linking immunoprecipitation and mass spectrometry approach, we found that DAZL bound to a large number of testicular mRNA transcripts (at least 3008) at the 3'-untranslated region and interacted with translation proteins including poly(A) binding protein. In the absence of DAZL, polysome-associated target transcripts, but not their total transcripts, were significantly decreased, resulting in a drastic reduction of an array of spermatogenic proteins and thus developmental arrest. Thus, DAZL is a master translational regulator essential for spermatogenesis.
()的表达是脊椎动物生殖细胞的一个标志,对胚胎生殖细胞的发育和分化至关重要,然而()的配子发生功能尚未完全阐明,其大多数直接靶点仍不清楚。我们发现,在小鼠生殖细胞中进行出生后阶段特异性的()缺失并不影响雌性生育能力,但会导致完全雄性不育,伴有精原干细胞逐渐丧失、减数分裂停滞和精子细胞停滞。通过交联免疫沉淀和质谱法进行全基因组高通量RNA测序,我们发现DAZL在3'-非翻译区与大量睾丸mRNA转录本(至少3008个)结合,并与包括多聚(A)结合蛋白在内的翻译蛋白相互作用。在没有DAZL的情况下,多聚核糖体相关的靶转录本而非其总转录本显著减少,导致一系列生精蛋白急剧减少,从而导致发育停滞。因此,DAZL是精子发生所必需的主要翻译调节因子。