The CCR4-NOT complex suppresses untimely translational activation of maternal mRNAs.

Control of mRNA poly(A) tail has central role to regulate mRNA metabolism: translation efficiency and mRNA stability. Gene expression in maturing oocytes largely relies on the regulation of mRNA metabolism as they are transcriptionally silent. The CCR4-NOT complex is a major deadenylase for mammals and regulates poly(A) tails of maternal mRNAs, however their function to translational regulation was not well understood. Here we show that CCR4-NOT suppresses translational activity of maternal mRNAs during oocyte maturation. Oocytes which lack entire deadenylase activity of CCR4-NOT by genetic deletion of its catalytic subunits: CNOT7 and CNOT8 showed increase of both expression of maternal mRNAs and translational activity of them during oocyte maturation. Comparative gene expression analysis using RNA-seq data from CNOT7&8 KO oocytes and Zp3-Cre control.mRNA poly(A)尾的调控在mRNA代谢调控中发挥核心作用，直接影响翻译效率与mRNA稳定性。成熟卵母细胞的基因表达在很大程度上依赖于mRNA代谢调控，因为该阶段细胞处于转录静默状态。CCR4-NOT复合物是哺乳动物体内的主要脱腺苷酸酶（deadenylase），可调控母源mRNA的poly(A)尾，但其在翻译调控中的功能尚未得到充分阐明。本研究证实，在卵母细胞成熟过程中，CCR4-NOT复合物可抑制母源mRNA的翻译活性。通过基因敲除其催化亚基CNOT7与CNOT8，使CCR4-NOT完全丧失脱腺苷酸酶活性的卵母细胞，在卵母细胞成熟过程中，其母源mRNA的表达水平与翻译活性均显著升高。本研究利用CNOT7与CNOT8基因敲除（Knockout, KO）卵母细胞及Zp3-Cre对照样本的RNA测序（RNA sequencing, RNA-seq）数据，开展了对比基因表达分析。