Translation initiation: structures, mechanisms and evolution

Abstract

Translation, the process of mRNA-encoded protein synthesis, requires a complex apparatus, composed of the ribosome, tRNAs and additional protein factors, including aminoacyl tRNA synthetases. The ribosome provides the platform for proper assembly of mRNA, tRNAs and protein factors and carries the peptidyl-transferase activity. It consists of small and large subunits. The ribosomes are ribonucleoprotein particles with a ribosomal RNA core, to which multiple ribosomal proteins are bound. The sequence and structure of ribosomal RNAs, tRNAs, some of the ribosomal proteins and some of the additional protein factors are conserved in all kingdoms, underlying the common origin of the translation apparatus. Translation can be subdivided into several steps: initiation, elongation, termination and recycling. Of these, initiation is the most complex and the most divergent among the different kingdoms of life. A great amount of new structural, biochemical and genetic information on translation initiation has been accumulated in recent years, which led to the realization that initiation also shows a great degree of conservation throughout evolution. In this review, we summarize the available structural and functional data on translation initiation in the context of evolution, drawing parallels between eubacteria, archaea, and eukaryotes. We will start with an overview of the ribosome structure and of translation in general, placing emphasis on factors and processes with relevance to initiation. The major steps in initiation and the factors involved will be described, followed by discussion of the structure and function of the individual initiation factors throughout evolution. We will conclude with a summary of the available information on the kinetic and thermodynamic aspects of translation initiation.

Crystal structure of the yeast eIF4A-eIF4G complex: An RNA-helicase controlled by protein–protein interactions

“…Although several 3D structures of individual components of the translation initiation machinery have been resolved (26,27), there is a lack of information of the structural features of protein-protein interactions at the atomic level. A number of reports have addressed the eIF4A-eIF4G interaction by isolating and characterizing mutants (6,7,(28)(29)(30)(31)).…”

Plant Cap-binding Complexes Eukaryotic Initiation Factors eIF4F and eIFISO4F

“…Initiation of protein synthesis requires the concerted effort of a large number of proteins and protein complexes, as well as multiple methods of control and control elements (1)(2)(3)(4)(5). Among the protein complexes required is eIF4F, the cap-binding complex, which binds to the m 7 G 2 cap found at the 5Ј end of most eukaryotic cellular mRNAs.…”

“…Mammalian eIF4G consists of several domains for interaction with these factors. The eIF4E and poly(A) binding protein binding sites are located in the N-terminal region, whereas the C-terminal region contains three HEAT domains, MIF4G (eIF4A and eIF3), MA3 (eIF4A), and W2 (MNK) (1,(13)(14)(15)(16)(17)(18). However, yeast eIF4G has only retained the MIF4G domain and lost the MA3 and W2 HEAT domains.…”

The Role of the Poly(A) binding protein in the assembly of the Cap-binding complex during translation initiation in plants

“…6,[15][16][17][18][19][20] The binding of eIF4A to the HEAT domains positions the 2 eIF4A domains containing the ATP-and RNAbinding sites in a partially closed state that facilitates interaction with substrates and the release of reaction products. 19,21,22 Binding of eIF4E to human eIF4G also stimulates eIF4A helicase activity by overcoming the autoinhibitory function of the eIF4E-binding site in eIF4G and the ability of eIF4E to do so is independent of its capbinding function.…”