BTG4 is a meiotic cell cycle-coupled maternal-zygotic-transition licensing factor in oocytes

BTG4 是卵母细胞中减数分裂细胞周期偶联的母体-合子转换许可因子

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作者:Chao Yu, Shu-Yan Ji, Qian-Qian Sha, Yujiao Dang, Jian-Jie Zhou, Yin-Li Zhang, Yang Liu, Zhong-Wei Wang, Boqiang Hu, Qing-Yuan Sun, Shao-Chen Sun, Fuchou Tang, Heng-Yu Fan

Abstract

The mRNAs stored in oocytes undergo general decay during the maternal-zygotic transition (MZT), and their stability is tightly interconnected with meiotic cell-cycle progression. However, the factors that trigger decay of maternal mRNA and couple this event to oocyte meiotic maturation remain elusive. Here, we identified B-cell translocation gene-4 (BTG4) as an MZT licensing factor in mice. BTG4 bridged CNOT7, a catalytic subunit of the CCR4-NOT deadenylase, to eIF4E, a key translation initiation factor, and facilitated decay of maternal mRNA. Btg4-null females produced morphologically normal oocytes but were infertile, owing to early developmental arrest. The intrinsic MAP kinase cascade in oocytes triggered translation of Btg4 mRNA stored in fully grown oocytes by targeting the 3' untranslated region, thereby coupling CCR4-NOT deadenylase-mediated decay of maternal mRNA with oocyte maturation and fertilization. This is a key step in oocyte cytoplasmic maturation that determines the developmental potential of mammalian embryos.

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