A MAPK cascade couples maternal mRNA translation and degradation to meiotic cell cycle progression in mouse oocytes

Area of Science:

• Reproductive biology
• Molecular and cell biology
• Developmental biology

Background:

• Mammalian oocyte maturation requires translational activation of maternal mRNAs.
• Cytoplasmic polyadenylation element binding protein 1 (CPEB1) is crucial for this process.
• The trigger for CPEB1 activation during oocyte maturation remains unknown.

Purpose of the Study:

• To elucidate the signaling pathway that activates CPEB1 during mammalian oocyte maturation.
• To investigate the role of mitogen-activated protein kinase (MAPK) in regulating maternal mRNA translation.
• To understand the mechanism linking ERK1/2 signaling to oocyte meiotic progression and the maternal-zygotic transition (MZT).

Main Methods:

• Investigated CPEB1 phosphorylation and degradation in mouse oocytes.
• Utilized site-directed mutagenesis to study CPEB1 phosphorylation and ubiquitin E3 ligase binding sites.
• Examined the effects of ERK1/2 knockout and DAZL overexpression on oocyte maturation.
• Assessed spindle assembly, mRNA translation, and meiotic arrest.

Main Results:

• A MAPK cascade, specifically ERK1/2, triggers CPEB1 phosphorylation and degradation.
• Mutations in CPEB1 phosphorylation or E3 ligase binding sites caused dominant-negative effects, impairing spindle assembly and mRNA translation.
• ERK1/2 knockout oocytes exhibited defects in meiotic progression and MZT.
• Overexpression of DAZL partially rescued meiotic defects in ERK1/2-deficient oocytes.

Conclusions:

• ERK1/2-mediated CPEB1 phosphorylation and degradation is a key mechanism for maternal mRNA translational activation.
• This pathway is essential for mouse oocyte maturation, including spindle assembly, metaphase II arrest, and the maternal-zygotic transition.
• ERK1/2 signaling is critical for initiating translation of maternal mRNAs required for early development.