Cargando…
A Retrospective on eIF2A—and Not the Alpha Subunit of eIF2
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 o...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139343/ https://www.ncbi.nlm.nih.gov/pubmed/32192132 http://dx.doi.org/10.3390/ijms21062054 |
_version_ | 1783518744032575488 |
---|---|
author | Komar, Anton A. Merrick, William C. |
author_facet | Komar, Anton A. Merrick, William C. |
author_sort | Komar, Anton A. |
collection | PubMed |
description | 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-tRNA(i) 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-tRNA(i) to 40S subunit in eukaryotes. It was found however, that eIF2A can promote recruitment of Met-tRNA(i) 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. |
format | Online Article Text |
id | pubmed-7139343 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71393432020-04-10 A Retrospective on eIF2A—and Not the Alpha Subunit of eIF2 Komar, Anton A. Merrick, William C. Int J Mol Sci Review 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-tRNA(i) 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-tRNA(i) to 40S subunit in eukaryotes. It was found however, that eIF2A can promote recruitment of Met-tRNA(i) 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. MDPI 2020-03-17 /pmc/articles/PMC7139343/ /pubmed/32192132 http://dx.doi.org/10.3390/ijms21062054 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Komar, Anton A. Merrick, William C. A Retrospective on eIF2A—and Not the Alpha Subunit of eIF2 |
title | A Retrospective on eIF2A—and Not the Alpha Subunit of eIF2 |
title_full | A Retrospective on eIF2A—and Not the Alpha Subunit of eIF2 |
title_fullStr | A Retrospective on eIF2A—and Not the Alpha Subunit of eIF2 |
title_full_unstemmed | A Retrospective on eIF2A—and Not the Alpha Subunit of eIF2 |
title_short | A Retrospective on eIF2A—and Not the Alpha Subunit of eIF2 |
title_sort | retrospective on eif2a—and not the alpha subunit of eif2 |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139343/ https://www.ncbi.nlm.nih.gov/pubmed/32192132 http://dx.doi.org/10.3390/ijms21062054 |
work_keys_str_mv | AT komarantona aretrospectiveoneif2aandnotthealphasubunitofeif2 AT merrickwilliamc aretrospectiveoneif2aandnotthealphasubunitofeif2 AT komarantona retrospectiveoneif2aandnotthealphasubunitofeif2 AT merrickwilliamc retrospectiveoneif2aandnotthealphasubunitofeif2 |