The mechanism of eukaryotic translation initiation and principles of its regulation

Protein synthesis is regulated at the initiation stage. Determining the structures and activities of initiation factors, and mapping their interactions in ribosomal initiation complexes, has advanced our understanding of translation initiation and provided a foundation for studying its regulation. Protein synthesis is principally regulated at the initiation stage (rather than during elongation or termination), allowing rapid, reversible and spatial control of gene expression. Progress over recent years in determining the structures and activities of initiation factors, and in mapping their interactions in ribosomal initiation complexes, have advanced our understanding of the complex translation initiation process. These developments have provided a solid foundation for studying the regulation of translation initiation by mechanisms that include the modulation of initiation factor activity (which affects almost all scanning-dependent initiation) and through sequence-specific RNA-binding proteins and microRNAs (which affect individual mRNAs).