We uncover how RNA influences the transition from the egg to a viable embryo.
Contact: Andrej Šušor
In cells, genetic information encoded in DNA is transcribed into mRNA, which is then translated into proteins. These proteins serve as the fundamental structural and regulatory components of the cell. The oocyte is a notable exception: at the onset of meiosis, its transcription (the formation of new RNA) nearly ceases. As a result, the oocyte relies entirely on previously accumulated mRNAs, translating them into essential proteins during meiosis. The precise spatial distribution of mRNAs within the large oocyte, and their translation at the correct time and place, is critical for the successful completion of meiosis. Errors in localization or timing of translation can lead to defective oocyte division and subsequent embryonic developmental disorders. Our goal is to understand these regulatory mechanisms, identify the key molecular players, and determine how their dysfunction contributes to reproductive disorders.
RNA-binding proteins (RBPs) are central to RNA fate within the cell, influencing its stability, localization, and translational potential. Among these, the CPEB protein is particularly important: it regulates mRNA translation by elongating the poly(A) tail, thereby enhancing ribosome recruitment and enabling protein synthesis at the appropriate time and location. In lower vertebrates, such as the clawed frog, CPEB activity is modulated by Aurora A kinase. However, our research indicates that this mechanism operates differently in mammals. Consequently, we are investigating other proteins that modulate CPEB and additional RBPs in mammalian oocytes. These proteins are essential not only for proper meiotic progression but also for successful embryonic development following fertilization. Disruptions in their regulation can have profound impacts on fertility and embryogenesis.
Our findings advance the understanding of the molecular mechanisms governing the early stages of mammalian reproduction. Detailed insights into these processes may inform new strategies for diagnosing and treating fertility disorders.
Figure 1. Visualization of active translation (red) in a growing mouse oocyte, essential for its growth and maturation to a stage competent for fertilization and capable of supporting preimplantation development in the maternal body. The key cytoskeletal complex F-actin is shown in green, extending through the zona pellucida to mediate communication between the oocyte and surrounding follicular cells. DNA is visualized in blue; its condensed structure indicates suppressed RNA synthesis, while transcripts generated in earlier stages are translated into proteins required for completion of meiotic maturation and the development of a preimplantation embryo competent for successful uterine implantation.
Figure 2: Live imaging of an oocyte and monitoring of its development after suppression of ANK2 synthesis.
The specific protein ANK2 is translated at the meiotic spindle, and its translation is essential for the proper formation of a mature, fertilization-competent oocyte. Blocking translation leads to defects in this process. Our results demonstrate that localized synthesis of ANK2 is crucial for normal oocyte development and physiological function. Arrows indicate abnormalities in oocyte division.
