Mammalian oocytes store mRNAs in a mitochondria-associated membraneless compartment

Area of Science:

• Cell Biology
• Developmental Biology
• Molecular Reproduction

Background:

• Full-grown oocytes are transcriptionally silent, relying on stored maternal messenger RNAs (mRNAs) for development.
• The precise location and mechanisms for maternal mRNA storage in mammalian oocytes remain largely unknown.

Purpose of the Study:

• To identify and characterize the storage site for maternal mRNAs in mammalian oocytes.
• To elucidate the molecular mechanisms regulating maternal mRNA localization, translation, and stability.

Main Methods:

• Immunofluorescence microscopy to visualize MARDO formation and ZAR1 localization.
• Mitochondrial membrane potential measurements.
• RNA immunoprecipitation followed by sequencing (RIP-Seq) to identify MARDO-associated mRNAs.
• ZAR1 knockout mouse model to assess MARDO function.

Main Results:

• Mammalian oocytes accumulate maternal mRNAs within a mitochondria-associated ribonucleoprotein domain (MARDO).
• MARDO formation is promoted by the RNA-binding protein ZAR1 and linked to increased mitochondrial membrane potential.
• MARDO functions as a hydrogel-like matrix, repressing mRNA translation and clustering mitochondria.
• Loss of ZAR1 disrupts MARDO, leading to mitochondrial dispersion and premature mRNA loss, impacting fertility.

Conclusions:

• A novel mitochondria-associated membraneless compartment, MARDO, is identified as the primary site for maternal mRNA storage in mammalian oocytes.
• MARDO plays a critical role in regulating mitochondrial distribution, maternal mRNA storage, translation, and decay.
• The ZAR1-dependent MARDO is essential for maintaining oocyte meiotic maturation and ensuring successful early embryonic development and fertility.