Requirement of the 3'-UTR-dependent suppression of DAZL in oocytes for pre-implantation mouse development.
Requirement of the 3'-UTR-dependent suppression of DAZL in oocytes for pre-implantation mouse development.
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DOI：
10.1371/journal.pgen.1007436
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发表时间：
2018-06
期刊：
影响因子：
4.5
通讯作者：
Saga Y
中科院分区：
文献类型：
--
作者：
Fukuda K;Masuda A;Naka T;Suzuki A;Kato Y;Saga Y
功能性卵母细胞通过复杂的分子和细胞过程产生。特别是，由RNA结合蛋白（RBP）介导的转录后基因调控的贡献对于在此过程中控制适当的基因表达至关重要。DAZL（deleted in azoospermia-like）是原始生殖细胞性分化和排卵卵母细胞减数分裂过程中所必需的RBP之一。然而，DAZL参与卵泡卵母细胞的发育仍然是未知的。在这里，我们发现Dazl在卵泡卵母细胞中以3′-UTR依赖的方式被抑制，并且这种抑制是正常的植入前发育所必需的。我们发现DAZL的抑制发生在出生后的卵母细胞中，伴随着原始卵泡的形成，而Dazl mRNA在整个卵母细胞发育过程中持续表达，这增加了DAZL对于卵泡卵母细胞的生存和生长不可或缺的可能性。事实上，卵泡卵母细胞特异性敲除Dazl导致产生正常数量的幼崽。另一方面，由于着床前发育缺陷，过表达DAZL的转基因雌性小鼠产生的幼崽数量少于对照组。我们的数据表明，DAZL在卵母细胞中的转录后抑制是控制功能卵母细胞发育中基因表达的重要机制。进化上保守的DAZ家族基因不可或缺地参与生殖系发育。Dazl基因是哺乳动物DAZ基因家族中的一员，在原始生殖细胞的性分化和精子发生中起重要作用，并参与排卵卵减数分裂II的进程。尽管它在生殖细胞发育过程中的多个过程中的重要性，它在卵泡卵母细胞发育中的参与是神秘的。本研究针对这一问题，发现DAZL在出生后卵母细胞中以3′-UTR依赖的方式被抑制。此外，这种抑制是受精后正常着床前发育所需的，这表明存在一种控制DAZL表达的未知机制。我们的数据提供了新的见解，转录后基因调控参与卵母细胞的发展。
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. Evolutionarily conserved DAZ family genes are indispensably involved in germline development. Dazl (deleted in azoospermia-like) is a member of the mammalian DAZ family of genes, and plays crucial roles in the sexual differentiation of primordial germ cells and spermatogenesis, and is implicated in the progression of meiosis II in ovulated eggs. Despite its importance for multiple processes during germline development, its participation in follicular oocyte development is enigmatic. This study addressed this issue and found that DAZL is translationally suppressed in postnatal oocytes in a 3′-UTR-dependent manner. Furthermore, this suppression is required for normal pre-implantation development after fertilization, suggesting the presence of an unidentified mechanism controlling DAZL expression. Our data provide new insights for post-transcriptional gene regulation involved in oocyte development.
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