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Updated: Jul 15, 2025

Determining the Role of Maternally-Expressed Genes in Early Development with Maternal Crispants
Published on: December 21, 2021
The CCR4-NOT complex suppresses untimely translational activation of maternal mRNAs
Shou Soeda1,2, Masaaki Oyama3, Hiroko Kozuka-Hata3
1Cell Signal Unit, Okinawa Institute of Science and Technology, Kunigami, 904-0495, Japan.
Abstract:
Control of mRNA poly(A) tails is essential for regulation of mRNA metabolism, specifically translation efficiency and mRNA stability. Gene expression in maturing oocytes relies largely on post-transcriptional regulation, as genes are transcriptionally silent during oocyte maturation. The CCR4-NOT complex is a major mammalian deadenylase, which regulates poly(A) tails of maternal mRNAs; however, the function of the CCR4-NOT complex in translational regulation has not been well understood. Here, we show that this complex suppresses translational activity of maternal mRNAs during oocyte maturation. Oocytes lacking all CCR4-NOT deadenylase activity owing to genetic deletion of its catalytic subunits, Cnot7 and Cnot8, showed a large-scale gene expression change caused by increased translational activity during oocyte maturation. Developmental arrest during meiosis I in these oocytes resulted in sterility of oocyte-specific Cnot7 and Cnot8 knockout female mice. We further showed that recruitment of CCR4-NOT to maternal mRNAs is mediated by the 3'UTR element CPE, which suppresses translational activation of maternal mRNAs. We propose that suppression of untimely translational activation of maternal mRNAs via deadenylation by CCR4-NOT is essential for proper oocyte maturation.
Insights
The CCR4-NOT complex, a key deadenylase, suppresses maternal mRNA translation during oocyte maturation. Its absence causes developmental arrest and sterility, highlighting its essential role in female fertility.
Area of Science:
- Molecular Biology
- Developmental Biology
- Gene Regulation
Background:
- Post-transcriptional regulation is crucial for gene expression in maturing oocytes, which are transcriptionally silent.
- The CCR4-NOT complex is a major mammalian deadenylase regulating mRNA poly(A) tail length, but its role in translational control during oocyte maturation was unclear.
Purpose of the Study:
- To investigate the function of the CCR4-NOT complex in the translational regulation of maternal mRNAs during oocyte maturation.
- To determine the consequences of CCR4-NOT deadenylase activity loss on oocyte development and female fertility.
Main Methods:
- Genetic deletion of CCR4-NOT catalytic subunits (Cnot7 and Cnot8) in oocytes.
- Analysis of gene expression changes and translational activity in knockout oocytes.
- Investigation of CCR4-NOT recruitment to maternal mRNAs via 3'UTR elements.
Main Results:
- Oocytes lacking CCR4-NOT deadenylase activity exhibited widespread gene expression changes due to increased translational activity.
- Deletion of Cnot7 and Cnot8 in oocytes led to developmental arrest during meiosis I and sterility in female mice.
- The CPE element in the 3'UTR mediates CCR4-NOT recruitment, suppressing maternal mRNA translation.
Conclusions:
- The CCR4-NOT complex is essential for suppressing premature translational activation of maternal mRNAs during oocyte maturation.
- Deadenylation by CCR4-NOT is critical for proper oocyte development and maintaining female fertility.
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