During the final stages of oocyte growth, these germ cells become transcriptionally inactive while preparing to resume meiosis and jumpstart their maturation into eggs. At this austere time, oocytes can only use maternal messenger RNAs (mRNAs) they have previously stored to get through their maturation process and early embryonic development if fertilized. Oocytes from the worm Caenorhabditis elegans store mRNA in P granules, those of fruit flies do so in polar granules, and aquatic frogs and zebrafish rely on a structure called the Balbiani body—all of which are membraneless organelles. But for mammals, the storage site has been terra incognita so far.
Maternal mRNA has previously been reported to be present in the cell’s cortex—a boundary zone that includes the cell membrane and cytoplasm—and the nucleus of mammalian oocytes, but without conclusive evidence that either of these cellular spaces is the site of RNA storage. A study published online today (October 20) in Science sheds light on the enigma, showing that these oocytes accumulate mRNA in a membraneless compartment that is associated with mitochondria. The study’s authors report that they observed this newly discovered structure in various mammalian species, including mice and humans.
Where mRNAs are localized in a fully grown mammalian oocyte has been a longstanding question, says coauthor Shiya Cheng, a cell biologist at the Max Planck Institute for Multidisciplinary Sciences in Germany. To answer it, he and his colleagues first used various staining techniques to establish that both RNA-binding proteins and mRNA are colocalized with mitochondria in mouse, pig, cow, and human oocytes. These molecules cluster around mitochondria throughout the cytoplasm, forming a structure the team named the mitochondria-associated ribonucleoprotein domain (MARDO). They observed that MARDO becomes more prominent as oocytes grow larger, and that its formation is dependent on the parallel increase in mitochondrial membrane potential.
MARDO (represented by RNA-binding protein ZAR1 in green) clustering around mitochondria (magenta)
Cheng and his colleagues further showed that the RNA-binding protein ZAR1, which had been previously associated with oocyte maturation and mRNA regulation, plays an essential role in both MARDO assembly and dissolution in mouse oocytes. In the team’s experiments, ZAR1 promoted MARDO coalescence and its association with mitochondria. Once the oocyte transforms into a fertilized egg and the embryo starts to grow, transcription is restored and maternal mRNAs are no longer needed to drive embryonic development. During this transition, the team found that ZAR1 is degraded by the proteosome, and with that, MARDO is dissolved.
The study’s results are “pretty solid” and its findings “very convincing,” says Elvan Böke, a cell biologist at the Centre for Genomic Regulation in Barcelona who was not involved in the study but collaborates with one of its coauthors on a different project.
Considering “how important they are for female reproduction, we know very little about oocytes,” she says, despite similarly important cells such as neurons and cardiomyocytes being studied more widely. Thus, “this is a step in the right direction,” she notes, and learning about the existence of this compartment will likely trigger more research in this area.