3 A Comparative View of Initiation Site Selection Mechanisms

Abstract

Before plunging into details of the various models for translation initiation and the roles of the initiation factor proteins, it is worth first asking the question: What does initiation really involve or how do we define the stage at which the initiation process has been completed and elongation takes over? Viewed in this way, initiation can be defined quite simply as the process in which a special initiator tRNA, formyl-Met-tRNA_f or Met-tRNA_i, is positioned in the P-site of a ribosome, which is itself located at the correct AUG codon (or in some cases, a non-AUG initiation codon) for translation of the downstream open reading frame (ORF). Here, P-site occupancy is defined in the usual way as reactivity toward puromycin. Quite apart from the distinctive formyl group in the case of prokaryotes, the initiator tRNA itself has several features distinguishing it from all other tRNAs, including Met-tRNA_m used for elongation (Seong and Rajbhandary 1987; Wakao et al. 1989), and as insertion of a charged tRNA into the P-site is an event unique to the initiation process, it is hardly surprising that this needs special protein factors, IF2 in prokaryotic systems and eIF2 in eukaryotes.

Apart from this feature of initiation common to both prokaryotes and eukaryotes, another universal characteristic is that the initiation process starts with separated ribosomal subunits (Guthrie and Nomura 1968; Howard et al. 1970; Blumberg et al. 1979). It is not entirely clear why this has to be the case. Perhaps efficient access of the initiator tRNA into...