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Publication : CNOT6L couples the selective degradation of maternal transcripts to meiotic cell cycle progression in mouse oocyte.

First Author  Sha QQ Year  2018
Journal  EMBO J Volume  37
Issue  24 PubMed ID  30478191
Mgi Jnum  J:270454 Mgi Id  MGI:6276385
Doi  10.15252/embj.201899333 Citation  Sha QQ, et al. (2018) CNOT6L couples the selective degradation of maternal transcripts to meiotic cell cycle progression in mouse oocyte. EMBO J 37(24)
abstractText  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.
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