Division of Mammalian Development, Genetic Strains Research Center, National Institute of Genetics, Mishima, Shizuoka, Japan.
Department of Genetics, SOKENDAI, Mishima, Shizuoka, Japan.
PLoS Genet. 2018 Jun 8;14(6):e1007436. doi: 10.1371/journal.pgen.1007436. eCollection 2018 Jun.
Functional oocytes are produced through complex molecular and cellular processes. In particular, the contribution of post-transcriptional gene regulation mediated by RNA-binding proteins (RBPs) is crucial for controlling proper gene expression during this process. DAZL (deleted in azoospermia-like) is one of the RBPs required for the sexual differentiation of primordial germ cells and for the progression of meiosis in ovulated oocytes. However, the involvement of DAZL in the development of follicular oocytes is still unknown. Here, we show that Dazl is translationally suppressed in a 3'-UTR-dependent manner in follicular oocytes, and this suppression is required for normal pre-implantation development. We found that suppression of DAZL occurred in postnatal oocytes concomitant with the formation of primordial follicles, whereas Dazl mRNA was continuously expressed throughout oocyte development, raising the possibility that DAZL is dispensable for the survival and growth of follicular oocytes. Indeed, follicular oocyte-specific knockout of Dazl resulted in the production of normal number of pups. On the other hand, genetically modified female mice that overexpress DAZL produced fewer numbers of pups than the control due to defective pre-implantation development. Our data suggest that post-transcriptional suppression of DAZL in oocytes is an important mechanism controlling gene expression in the development of functional oocytes.
功能性卵子是通过复杂的分子和细胞过程产生的。特别是,RNA 结合蛋白(RBPs)介导的转录后基因调控对控制这个过程中适当的基因表达至关重要。DAZL(无精子症样缺失)是原始生殖细胞性分化和排卵卵子减数分裂进展所必需的 RBPs 之一。然而,DAZL 参与滤泡卵子的发育仍然未知。在这里,我们表明 Dazl 在滤泡卵子中以 3'-UTR 依赖的方式被翻译抑制,这种抑制对于正常的着床前发育是必需的。我们发现,DAZL 的抑制作用发生在出生后卵子伴随着原始卵泡的形成时,而 Dazl mRNA 在整个卵子发育过程中持续表达,这表明 DAZL 对于滤泡卵子的存活和生长不是必需的。事实上,滤泡卵子特异性敲除 Dazl 导致正常数量的幼崽的产生。另一方面,由于着床前发育缺陷,过度表达 DAZL 的基因修饰雌性小鼠产生的幼崽数量少于对照。我们的数据表明,卵子中 DAZL 的转录后抑制是控制功能性卵子发育中基因表达的重要机制。