eIF4B mRNA Translation Contributes to Cleavage Dynamics in Early Sea Urchin Embryos

Simple Summary Cell division, also known as mitosis, relies on a complex cascade of molecular events that orchestrates the whole process and decides when cells can start dividing. A key factor in this process is protein synthesis, which is carefully regulated inside the cell to assure the timely production of all the proteins required for mitosis. The embryos of sea urchins divide rapidly after fertilization and represent an informative model to analyze the role of protein synthesis regulation during cell cycle progression. For example, the analysis in the 1980s of sea urchin embryos fostered the discovery of Cyclin B, the first representative of a family of proteins that plays a universal role in controlling cell division. This finding was awarded in 2001 with the Nobel Prize in Physiology and Medicine. However, much remains to be learned, and how protein synthesis controls the time and speed of mitosis in a developing embryo is still unclear. For instance, discovering whether the translation of other mRNAs than mitotic cyclins is required to finely regulate the rate of embryonic cleavage has never been tested. In this work, we investigated the role of the translation of an mRNA encoding a protein called eIF4B in the dynamics of embryonic cell division. We showed that newly synthesized eIF4B directly impacts cell division rates in two sea urchin species. Cell divisions are delayed when the production of eIF4B is inhibited in a fertilized egg. Conversely, increased production of eIF4B accelerates mitosis. Therefore, eIF4B mRNA translation represents a new means to regulate the pace of embryonic cleavages. Moreover, since eIF4B is a translational regulator, our findings suggest that the function of its mRNA translation is boosting the production of other proteins essential for mitosis. The cells of the sea urchin embryos seem thus equipped with a controlling device capable of modulating cell division rates, a molecular switch that could contribute to coordinating the first steps of development in other animals as well. During the first steps of sea urchin development, fertilization elicits a marked increase in protein synthesis essential for subsequent cell divisions. While the translation of mitotic cyclin mRNAs is crucial, we hypothesized that additional mRNAs must be translated to finely regulate the onset into mitosis. One of the maternal mRNAs recruited onto active polysomes at this stage codes for the initiation factor eIF4B. Here, we show that the sea urchin eIF4B orthologs present the four specific domains essential for eIF4B function and that Paracentrotus lividus eIF4B copurifies with eIF4E in a heterologous system. In addition, we investigated the role of eIF4B mRNA de novo translation during the two first embryonic divisions of two species, P. lividus and Sphaerechinus granularis. Our results show that injection of a morpholino directed against eIF4B mRNA results in a downregulation of translational activity and delays cell division in these two echinoids. Conversely, injection of an mRNA encoding for P. lividus eIF4B stimulates translation and significantly accelerates cleavage rates. Taken together, our findings suggest that eIF4B mRNA de novo translation participates in a conserved regulatory loop that contributes to orchestrating protein synthesis and modulates cell division rhythm during early sea urchin development.

Automated summary

Cell division, or mitosis, relies on protein synthesis to regulate the timing and speed of the process. Sea urchin embryos are a useful model for studying this regulation. In this study, the researchers investigated the role of eIF4B mRNA translation in embryonic cell division. They found that inhibiting eIF4B synthesis delayed cell division, while increasing eIF4B production accelerated mitosis. This suggests that eIF4B mRNA translation is a new means of regulating the pace of embryonic cleavages, and it may also boost the production of other proteins essential for mitosis.