A Review of the Uncertainties of Eukaryotic Translation Initiation

This article proposes three possible explanations that relate to the process of eukaryotic translation initiation. These explanations suggest mechanisms as to how concentrations of initiation factors (by mass or by posttranslational modification) can influence start site selection, how regulation of translation by 4E-BP (an inhibitor of m⁷G cap-dependent translation) can be explained by "eIF4F disassembly" and how the scanning mechanism might involve initiation factor binding at the 5' end of the mRNA to provide for apparent unidirectional Brownian movement to locate the initiating AUG. These represent testable models, although the experiments would not be simple. It is hoped that the insights provided will assist researchers in defining the precise steps and mechanisms of the complex initiation process. It is noted that the better this process is understood, the easier it will be to understand how this process is regulated under a wide variety of biological situations, such as nutritional deprivation, heat shock, cell growth, or disease. Additionally, as initiation is the rate-limiting step in translation, a better understanding of this process should also suggest new avenues to treat various diseases, especially conditions of unrestricted growth.