Abstract
Initiation of protein synthesis in eukaryotes is a complex process requiring more than 12 different initiation factors, comprising over 30 polypeptide chains. The functions of many of these factors have been established in great detail; however, the precise role of some of them and their mechanism of action is still not well understood. Eukaryotic initiation factor 2A (eIF2A) is a single chain 65 kDa protein that was initially believed to serve as the functional homologue of prokaryotic IF2, since eIF2A and IF2 catalyze biochemically similar reactions, i.e., they stimulate initiator Met-tRNAi binding to the small ribosomal subunit. However, subsequent identification of a heterotrimeric 126 kDa factor, eIF2 (α,β,γ) showed that this factor, and not eIF2A, was primarily responsible for the binding of Met-tRNAi to 40S subunit in eukaryotes. It was found however, that eIF2A can promote recruitment of Met-tRNAi to 40S/mRNA complexes under conditions of inhibition of eIF2 activity (eIF2α-phosphorylation), or its absence. eIF2A does not function in major steps in the initiation process, but is suggested to act at some minor/alternative initiation events such as re-initiation, internal initiation, or non-AUG initiation, important for translational control of specific mRNAs. This review summarizes our current understanding of the eIF2A structure and function.
Highlights
Translation is the final step of expression of genetic information and is commonly separated into four phases: initiation, elongation, termination and ribosome recycling [1,2,3]
The proper selection of the initiation codon depends on direct interaction between the small (30S) ribosomal subunit and the messenger RNA (mRNA) aided by the three single subunit initiation factors IF1, IF2, and IF3
This review summarizes our current understanding of the structure and function of a single subunit eukaryotic initiation factor 2A, that was initially believed to serve as the functional homologue of prokaryotic IF2, since Eukaryotic initiation factor 2A (eIF2A) and IF2 were shown to catalyze biochemically similar reactions, i.e., they stimulated initiator methionyl-transfer RNA (tRNA) (Met-tRNAi) binding to the small ribosomal subunit in response to AUG codon [22,24]
Summary
Translation (protein synthesis) is the final step of expression of genetic information and is commonly separated into four phases: initiation, elongation, termination and ribosome recycling [1,2,3]. The use of the poly(U)-directed synthesis of polyphenylalanine Mg2+ shift assay revealed that the elongation factors eEF1A and eEF2, and some other proteins (later to be identified as eIF1A, eIF5A and eIF5B) are required for this process [22,47] With these assays as the basis for activity determination, there have been multiple reports on the partial or complete purification of a variety of proteins of different molecular composition and weight capable of binding of initiator tRNAi to the 40S ribosomal subunit in an AUG-dependent manner (similar to that of the bacterial IF2) (Table 1). Met-tRNAi Phe-tRNAE.coli eIF2D Ref. [59,60] Met-tRNAi Phe-tRNA tRNAMeti (non-acylated)
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