Initiation of Translation

Translation initiation is a complex sequence of events required to start protein synthesis. This process requires the initiator tRNA (Met-tRNAi), the small (40S) and the large (60S) ribosomal subunits to assemble into an 80S ribosome at the initiation codon of mRNA (AUG) and is supported by eukaryotic initiation factors (eIFs). Briefly, the cap-binding complex eIF4F and the factors eIF4A and eIF4B are required for binding of 43S complexes (comprising a 40S subunit, eIF2/GTP/Met-tRNAi and eIF3) to the 5′ end of capped mRNA but are not sufficient to promote ribosomal scanning to the initiation codon. eIF1A enhances the ability of eIF1 to dissociate aberrantly assembled complexes from mRNA, and these factors synergistically mediate 48S complex assembly at the initiation codon. Joining of 48S complexes to 60S subunits to form 80S ribosomes requires eIF5B, which has an essential ribosome-dependent GTPase activity and hydrolysis of eIF2-bound GTP induced by eIF5.