Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, USA.
Biol Reprod. 2019 May 1;100(5):1147-1157. doi: 10.1093/biolre/ioz034.
Transcription ceases upon stimulation of oocyte maturation and gene expression during oocyte maturation, fertilization, and early cleavage relies on translational activation of maternally derived mRNAs. Two key mechanisms that mediate translation of mRNAs in oocytes have been described in detail: cytoplasmic polyadenylation-dependent and -independent. Both of these mechanisms utilize specific protein complexes that interact with cis-acting sequences located on 3'-untranslated region (3'-UTR), and both involve embryonic poly(A) binding protein (EPAB), the predominant poly(A) binding protein during early development. While mechanistic details of these pathways have primarily been elucidated using the Xenopus model, their roles are conserved in mammals and targeted disruption of key regulators in mouse results in female infertility. Here, we provide a detailed account of the molecular mechanisms involved in translational activation during oocyte and early embryo development, and the role of EPAB in this process.
转录在卵母细胞成熟的刺激下停止,卵母细胞成熟、受精和早期卵裂过程中的基因表达依赖于母体来源的 mRNA 的翻译激活。详细描述了两种介导卵母细胞中 mRNA 翻译的关键机制:细胞质多聚腺苷酸化依赖和非依赖。这两种机制都利用了与位于 3'非翻译区 (3'-UTR) 上的顺式作用序列相互作用的特定蛋白质复合物,并且都涉及胚胎多聚(A)结合蛋白 (EPAB),这是早期发育过程中主要的多聚(A)结合蛋白。虽然这些途径的机制细节主要是使用非洲爪蟾模型阐明的,但它们在哺乳动物中的作用是保守的,并且在小鼠中靶向破坏关键调节因子会导致雌性不育。在这里,我们详细描述了卵母细胞和早期胚胎发育过程中翻译激活所涉及的分子机制,以及 EPAB 在这一过程中的作用。