Translation Initiation Models in Prokaryotes and Eukaryotes

Abstract

Abstract Translation is one stage of protein synthesis in which messenger ribonucleic acid (mRNA) acts as a template for the synthesis of a polypeptide chain; it consists of four phases: initiation, elongation, termination and ribosome recycling. Initiation of protein synthesis, entailing ribosomal recognition of the mRNA start codon and the setting of the correct reading frame, is the rate‐limiting step of translation and the main target of translation regulation in all cells. However, the mechanism and molecular machinery for initiation have diverged in the primary domains of life: the Bacteria, the Archaea and the Eukarya (eukaryotes). In bacteria, translation initiation is relatively simple, while in eukaryotes is complex and requires more components. In archaea, despite their prokaryotic phenotype, the machinery for protein synthesis initiation is much more elaborated than in bacteria and presents intriguing similarities with the corresponding eukaryotic process. The features of translational initiation in archaea, bacteria and eukaryotes are reviewed, highlighting the divergent and common aspects of this important cellular process in the three domains of life. Key concepts Initiation is the first of four steps of the translation cycle. During initiation the small ribosomal subunit interacts with the messenger ribonucleic acid (mRNA) and finds the right start codon, thereby setting the correct reading frame for decoding. In all cells, translation initiation is assisted and modulated by several proteins called translation initiation factors (IFs). The most important roles of the IFs are to select the proper initiator transfer RNA, to adjust it correctly in the ribosomal P site, to ensure the accurate selection of the start codon and to prevent the premature joining of the large ribosomal subunit to the pre‐initiation complex. Initiation is the rate‐limiting step of translation. It is the efficiency whereby an mRNA is decoded and the amount of final product is largely determined at the initiation level. In all cells, the principal mechanisms of translational control act at the level of initiation, usually targeting certain IFs that play essential roles in the initiation process. The initiation step of translation has incurred a marked evolutionary divergence. The mechanism and components of initiation differ in several aspects in the three primary domains of life, that is the Bacteria, the Archaea and the Eukaryotes. The Bacteria have the simplest machinery for translation initiation. However, this is not because they are prokaryotes. The other prokaryotic domain, the Archaea, has a fairly complex machinery for initiation, resembling that of eukaryotes, which have the most complex initiation process.