ZAR1 and ZAR2 are required for oocyte meiotic maturation by regulating the maternal transcriptome and mRNA...

Area of Science:

• Developmental Biology
• Molecular Biology
• Genetics

Background:

• Zar1 is an early maternal-effect gene essential for mammalian embryonic development.
• Zar1-null embryos arrest before zygotic genome activation, but the mechanism is unknown.
• The role of Zar1 in oocyte maturation remains poorly understood.

Purpose of the Study:

• To investigate the function of Zar1 and its homolog Zar2 in mouse oocyte meiotic maturation.
• To elucidate the molecular mechanisms underlying Zar1/2's role in early embryonic development.

Main Methods:

• Gene knockout of Zar1 and Zar2 in mice.
• Analysis of oocyte meiotic progression, spindle formation, and chromosome aneuploidy.
• Quantification of maternal mRNA levels and protein synthesis.
• Investigation of mRNA-protein interactions and translational regulation.

Main Results:

• Zar1/2 deletion caused delayed meiotic resumption and abnormal spindle formation.
• Oocytes lacking Zar1/2 showed reduced maternal mRNA levels and protein synthesis.
• Impaired translational activation of key maturation proteins (cyclin B1, WEE2, BTG4) and abolished maternal-to-zygotic transition (MZT).
• ZAR1/2 directly regulate mRNA translation via 3'-UTRs and interact with proteins like MSY2.

Conclusions:

• Zar1/2 play a critical, previously unrecognized role in regulating the maternal transcriptome and translational activation during oocyte maturation.
• These findings challenge the traditional view of Zar1 function, extending its role to pre-fertilization events.
• Disruption of Zar1/2 function leads to impaired oocyte maturation and failure of MZT, impacting early development.