Organization and expression of zebrafish translation initiation factor 4E (EIF4E)

The regulation of protein synthesis is critical to a diversity of cellular processes. Translational control coordinates and regulates gene expression during such fundamental cellular processes as proliferation, differentiation, and metabolic homeostasis. It also plays a pivotal role in regulating gene expression during embryogenesis. The controlled synthesis of proteins is required to properly specify embryonic axis and tissue identity in vertebrates and invertebrates alike. The regulated translation of mRNAs involved in signal transduction and cell cycle control provides a sensitive mechanism for coordinating autocrine and paracrine signaling processes during embryonic development. The major regulatory checkpoint for protein synthesis is at the level of initiation. In a precisely controlled process, specific mRNA molecules are selected from a complex cytoplasmic mixture and recruited to the translational machinery. Translation of an mRNA initiates when it associates with a complex of proteins termed eIF4F. This interaction is required to reduce mRNA secondary structure and allow binding of the small ribosomal subunit. The limiting component of this complex, eIF4E, binds directly the 7-methyl-guanosine residue at the 5$spprime$-end of most eukaryotic mRNAs. As a cell-cycle regulator, the amount and activity of eIF4E is under strict control. Deregulation of eIF4E levels in cultured cells leads to either cell death or transformation. The importance of eIF4E expression in the developing embryo is presently unknown. Understanding the regulation and expression of the eIF4E gene is key to predicting its role in the regulation of embryonic gene expression. I have cloned the zebrafish eIF4E (zeIF4E) gene and characterized its expression during development. The zeIF4E gene encodes two mRNA splice-forms whose relative levels may regulate protein synthesis in the embryo, by controlling production of eIF4E protein. Molecular analyses and in situ hybridization reveal a potential role for eIF4E in regulating cellular proliferation in axial mesoderm, the neural keel, tailbud, and erythroid progenitors. The zeIF4E promoter contains transcriptional response elements likely to mediate the enriched expression of eIF4E in these tissues. Expression of zeIF4E in these cell-types may reflect a requirement for translational control in their development.