Study of Oocyte-To-Embryo Transition Regulators, OMA-1 and OMA-2 in C. Elegans
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A non-dividing, developmentally dormant oocyte is transformed into a rapidly dividing, differentiating embryo during a short period termed oocyte-to-embryo transition. Oocyte-to-embryo transition encompasses oocyte maturation and fertilization and is characterized by both cell cycle and developmental events. Understanding the mechanisms underlying oocyte-to-embryo transition is a fundamental goal for developmental biology and reproductive medicine. However, our current understanding of the transition is very limited. Two CCCH Tis-11 type zinc finger proteins of C. elegans, OMA-1 and OMA-2 are expressed exclusively in oocytes and 1-cell embryos, and are rapidly degraded at the first mitosis. Previous studies suggested that oma-1 and oma-2 are redundantly required for oocyte maturation, and the degradation of OMA-1/2 proteins at the end of the 1-cell stage is essential for embryogenesis. However, their roles in the 1-cell embryo, and the mechanism of the OMA-1/2 degradation were elusive. In addition, the molecular functions of OMA-1/2 proteins were unknown. In this study, I investigated the mechanism controlling OMA-1/2 degradation as well as the molecular and genetic functions of OMA-1/2. I showed that two proline directed kinases, MBK-2/DYRK2 and GSK-3 directly and likely sequentially phosphorylate OMA-1/2 to mark them for degradation at the end of the 1-cell stage. My data further suggest that SCF and/or ECS E3 ubiquitin ligase and the proteasome are likely responsible for the execution of OMA-1/2 degradation. Secondly, I characterized the molecular and genetic functions of OMA-1/2 in oocytes and 1-cell stage embryos. My data suggest that OMA-1/2 regulate multiple processes. These processes include transcription and translation. At the 1-cell stage, transcription is inactive. My data suggest that OMA-1/2 render 1-cell embryos transcriptionally quiescence by preventing the nuclear localization of a general transcription factor, TAF-4. OMA-1/2 (oma-1/2) interact with translational regulators, MEX-3 and SPN-4 physically, and other translation factors, puf-3/5/8, and cpb-3 genetically, suggesting that OMA-1/2 also regulate translation in oocytes and 1-cell embryos. In summary, my study revealed that phosphorylation and ubiquitination events regulate the degradation of OMA-1/2 proteins, and provided insights into functions of OMA-1/2 during oocyte-to-embryo transition.