Initiation of Protein Synthesis

Translation Initiation in Eukaryotes

A systemic analysis of translation initiation and the current mechanistic models of the initiation process. Initiation factors, their structures, activities and mechanisms of action in initiation and subsequent presentation of the tRNA mimicry hypothesis, applied to initiation factors is proposed. Ribosomal RNAs, their involvement and functional sites in initiation are displayed. The scanning model of initiation is described, as well as exceptions to the model. A view of IRES sequences and their relevance is communicated. Regulation of translation initiation and a discussion of the evolutionary aspects of the initiation system are final thoughts presented in the discussion.

A Simplified Overview of Eukaryotic Translation Initiation

The mechanism of eukaryotic translation initiation is unique compared to the prokaryotic process, due to the small 40S ribosomal subunit entering at the 5' end of the the mRNA, rather than recognizing immediately the start AUG codon. This is due to the lack of a Shine-Delgano sequence in eukaryotes, which is present in prokaryotes to recruit ribosomes. The 40S ribosomal subunit, along with the initiator Met-tRNAi-elF2-GTP and additional factors, migrate through the 5'untranslated region until meeting the first AUG codon. The AUG codon is recognized by its complementary anticodon present on the initiator tRNA through base-pairing (Cigan et al., 1988a). Forming a fixed complex at the start codon is mediated through the binding of 60S ribosomal subunit to the attached 40S complex (mechanistic differences in models will be mentioned later). Once complexed, initiation of translation begins, with ribosome creating the first peptide bond of the nascent protein.