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eIF2A, an initiator tRNA carrier refractory to eIF2 kinases, functions synergistically with eIF5B

Title
eIF2A, an initiator tRNA carrier refractory to eIF2 kinases, functions synergistically with eIF5B
Authors
Kim, EunahKim, Joon HyunSeo, KeunheeHong, Ka YoungAn, Seon Woo A.Kwon, JunyoungLee, Seung-Jae V.Jang, Sung Key
POSTECH Authors
Lee, Seung-Jae V.Jang, Sung Key
Date Issued
Dec-2018
Publisher
SPRINGER BASEL AG
Abstract
The initiator tRNA (Met-tRNA(i)(Met)) at the P site of the small ribosomal subunit plays an important role in the recognition of an mRNA start codon. In bacteria, the initiator tRNA carrier, IF2, facilitates the positioning of Met-tRNAiMet on the small ribosomal subunit. Eukarya contain the Met-tRNAiMet carrier, eIF2 (unrelated to IF2), whose carrier activity is inhibited under stress conditions by the phosphorylation of its -subunit by stress-activated eIF2 kinases. The stress-resistant initiator tRNA carrier, eIF2A, was recently uncovered and shown to load Met-tRNAiMet on the 40S ribosomal subunit associated with a stress-resistant mRNA under stress conditions. Here, we report that eIF2A interacts and functionally cooperates with eIF5B (a homolog of IF2), and we describe the functional domains of eIF2A that are required for its binding of Met-tRNAiMet, eIF5B, and a stress-resistant mRNA. The results indicate that the eukaryotic eIF5B-eIF2A complex functionally mimics the bacterial IF2 containing ribosome-, GTP-, and initiator tRNA-binding domains in a single polypeptide.
The initiator tRNA (Met-tRNA(i)(Met)) at the P site of the small ribosomal subunit plays an important role in the recognition of an mRNA start codon. In bacteria, the initiator tRNA carrier, IF2, facilitates the positioning of Met-tRNAiMet on the small ribosomal subunit. Eukarya contain the Met-tRNAiMet carrier, eIF2 (unrelated to IF2), whose carrier activity is inhibited under stress conditions by the phosphorylation of its -subunit by stress-activated eIF2 kinases. The stress-resistant initiator tRNA carrier, eIF2A, was recently uncovered and shown to load Met-tRNAiMet on the 40S ribosomal subunit associated with a stress-resistant mRNA under stress conditions. Here, we report that eIF2A interacts and functionally cooperates with eIF5B (a homolog of IF2), and we describe the functional domains of eIF2A that are required for its binding of Met-tRNAiMet, eIF5B, and a stress-resistant mRNA. The results indicate that the eukaryotic eIF5B-eIF2A complex functionally mimics the bacterial IF2 containing ribosome-, GTP-, and initiator tRNA-binding domains in a single polypeptide.
Keywords
eukaryotic initiation factor 5B; initiation factor; initiation factor 2alpha; unclassified drug; Caenorhabditis elegans protein; eukaryotic initiation factor-5B; initiation factor; initiation factor 2; methionine transfer RNA; protein binding; protein kinase R; amino acid sequence; Article; complex formation; controlled study; gene interaction; molecular evolution; protein binding; protein domain; protein expression; protein function; protein protein interaction; translation initiation; animal; Caenorhabditis elegans; genetics; HEK293 cell line; human; metabolism; mutation; RNA interference; sequence homology; Western blotting; Amino Acid Sequence; Animals; Blotting, Western; Caenorhabditis elegans; Caenorhabditis elegans Proteins; eIF-2 Kinase; Eukaryotic Initiation Factor-2; Eukaryotic Initiation Factors; HEK293 Cells; Humans; Mutation; Protein Binding; RNA Interference; RNA, Transfer, Met; Sequence Homology, Amino Acid
URI
http://oasis.postech.ac.kr/handle/2014.oak/94482
DOI
10.1007/s00018-018-2870-4
ISSN
1420-682X
Article Type
Article
Citation
CELLULAR AND MOLECULAR LIFE SCIENCES, vol. 75, no. 23, page. 4287 - 4300, 2018-12
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 LEE, SEUNG JAE
Dept of Life Sciences
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