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.

Development (Cambridge, England)
|September 28, 2023
PubMed

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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