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An oocyte-specific ELAVL2 isoform is a translational repressor ablated from meiotically competent antral oocytes

机译:卵母细胞特异性的ELAVL2亚型是一种从减数分裂感受态窦房卵母细胞上去除的翻译阻遏物

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摘要

At the end of the growth phase, mouse antral follicle oocytes acquire full developmental competence. In the mouse, this event is marked by the transition from the so-called non-surrounded nucleolus (NSN) chromatin configuration into the transcriptionally quiescent surrounded nucleolus (SN) configuration, which is named after a prominent perinucleolar condensed chromatin ring. However, the SN chromatin configuration alone is not sufficient for determining the developmental competence of the SN oocyte. There are additional nuclear and cytoplamic factors involved, while a little is known about the changes occurring in the cytoplasm during the NSN/SN transition. Here, we report functional analysis of maternal ELAVL2 an AU-rich element binding protein. Elavl2 gene encodes an oocyte-specific protein isoform (denoted ELAVL2°), which acts as a translational repressor. ELAVL2° is abundant in fully grown NSN oocytes, is ablated during the NSN/SN transition and remains low during the oocyte-to-embryo transition (OET). ELAVL2° overexpression during meiotic maturation causes errors in chromosome segregation, indicating the significance of naturally reduced ELAVL2° levels in SN oocytes. On the other hand, during oocyte growth, prematurely reduced Elavl2 expression results in lower yields of fully grown and meiotically matured oocytes, suggesting that Elavl2 is necessary for proper oocyte maturation. Moreover, Elavl2 knockdown showed stimulating effects on translation in fully grown oocytes. We propose that ELAVL2 has an ambivalent role in oocytes: it functions as a pleiotropic translational repressor in efficient production of fully grown oocytes, while its disposal during the NSN/SN transition contributes to the acquisition of full developmental competence.
机译:在生长阶段结束时,小鼠窦卵泡卵母细胞获得完全的发育能力。在小鼠中,此事件的特征是从所谓的非环绕核仁(NSN)染色质构型过渡到转录静止的包围核仁(SN)构型,该构型以突出的核仁周围染色质环命名。然而,仅SN染色质构型不足以确定SN卵母细胞的发育能力。还涉及其他核和细胞增生因子,而对NSN / SN转换过程中细胞质中发生的变化知之甚少。在这里,我们报告母ELAVL2,一种富含AU的元素结合蛋白的功能分析。 Elavl2基因编码一个卵母细胞特异性蛋白同工型(表示为ELAVL2°),其充当翻译阻遏物。 ELAVL2°在完全生长的NSN卵母细胞中丰富,在NSN / SN过渡过程中被消融,而在卵母细胞-胚胎过渡(OET)期间保持较低。减数分裂成熟过程中的ELAVL2°过表达会导致染色体分离错误,这表明SN卵母细胞中ELAVL2°水平自然降低的重要性。另一方面,在卵母细胞生长期间,过早降低的Elavl2表达导致完全生长和减数分裂成熟的卵母细胞的产量降低,这表明Elavl2对于适当的卵母细胞成熟是必要的。此外,Elavl2组合件显示出对完全生长的卵母细胞中翻译的刺激作用。我们提出,ELAVL2在卵母细胞中具有矛盾的作用:它在有效生产完全生长的卵母细胞中起多效性翻译阻遏物的作用,而在NSN / SN过渡期将其丢弃有助于获得完整的发育能力。

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