CNOT6L couples the selective degradation of maternal transcripts to meiotic cell cycle progression in mouse oocyte. (26th November 2018)

• Record Type: Journal Article
• Authors: Sha, Qian‐Qian; Yu, Jia‐Li; Guo, Jing‐Xin; Dai, Xing‐Xing; Jiang, Jun‐Chao; Zhang, Yin‐Li; Yu, Chao; Ji, Shu‐Yan; Jiang, Yu; Zhang, Song‐Ying; Shen, Li; Ou, Xiang‐Hong; Fan, Heng‐Yu
• Is Part Of: EMBO journal. Volume 37:Number 24(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-11-26
• Subjects: CCR4–NOT -- maternal mRNA decay -- maternal‐to‐zygotic transition -- meiotic maturation -- oocyte; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.201899333
• Languages: English
• ISSNs: 0261-4189

Abstract

Abstract: Meiotic resumption‐coupled degradation of maternal transcripts occurs during oocyte maturation in the absence of mRNA transcription. The CCR4–NOT complex has been identified as the main eukaryotic mRNA deadenylase. In vivo functional and mechanistic information regarding its multiple subunits remains insufficient. Cnot6l, one of four genes encoding CCR4–NOT catalytic subunits, is preferentially expressed in mouse oocytes. Genetic deletion of Cnot6l impaired deadenylation and degradation of a subset of maternal mRNAs during oocyte maturation. Overtranslation of these undegraded mRNAs caused microtubule–chromosome organization defects, which led to activation of spindle assembly checkpoint and meiotic cell cycle arrest at prometaphase. Consequently, Cnot6l −/− female mice were severely subfertile. The function of CNOT6L in maturing oocytes is mediated by RNA‐binding protein ZFP36L2, not maternal‐to‐zygotic transition licensing factor BTG4, which interacts with catalytic subunits CNOT7 and CNOT8 of CCR4–NOT. Thus, recruitment of different adaptors by different catalytic subunits ensures stage‐specific degradation of maternal mRNAs by CCR4–NOT. This study provides the first direct genetic evidence that CCR4–NOT‐dependent and particularly CNOT6L‐dependent decay of selective maternal mRNAs is a prerequisite for meiotic maturation of oocytes. Synopsis: Maternal transcripts are degraded during oocyte maturation. A new mouse model demonstrates that Cnot6l, one of four genes encoding catalytic subunits of the mRNA deadenylation complex CCR4–NOT, is preferentially expressed in oocytes and mediates meiosis‐coupled maternal mRNA decay. Genetic deletion of Cnot6l impaired deadenylation and degradation of a subset of maternal mRNAs during mouse oocyte maturation. Cnot6l ‐deficient female mice were severely subfertile. Aberrant translation of undegraded mRNAs in the Cnot6l knockout caused microtubule–chromosome organization defects, activation of spindle assembly checkpoint and meiotic cell cycle arrest at prometaphase. Recruitment of distinct RNA‐binding adaptor proteins by different CCR4–NOT subunits ensures stage‐specific degradation of maternal mRNAs. CNOT6L and other CCR4–NOT components are important downstream effectors of ERK1 and ERK2 in regulating spindle assembly and meiotic cell cycle progression in oocytes. Abstract : A new mouse model shows that the CCR4‐NOT complex ensures timely clearance of maternal mRNAs in developing oocytes, thereby preventing aberrant translation and meiotic defects.