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Actin Bundling Mutants in Translation Elongation Factor 1A Induce Altered Protein Synthesis at both the Initiation and Elongation Steps
Author(s) -
Perez Winder B,
Kinzy Terri G.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.986.2
Subject(s) - elongation factor , elongation , translation (biology) , mutant , actin , eukaryotic translation , protein biosynthesis , microbiology and biotechnology , eukaryotic translation elongation factor 1 alpha 1 , eukaryotic initiation factor , initiation factor , biology , eif2 , cytoskeleton , biochemistry , rna , messenger rna , cell , ribosome , gene , materials science , ultimate tensile strength , metallurgy
Apart from its canonical function in translation elongation, eukaryotic translation elongation factor 1A (eEF1A) has been shown to interact with the actin cytoskeleton. Amino acid substitutions in eEF1A that reduce its ability to bind and bundle actin in vitro , cause improper actin organization in vivo , as well as reduce total translation. Although initial analysis indicated the reduced translation was through initiation, in vitro analysis of the mutant proteins shows changes at the level of elongation. These strains exhibit increased levels of phosphorylated initiation factor 2α (eIF2α), suggesting the involvement of the Gcn2p protein kinase. Gcn2p is a key regulator of the general amino acid control (GAAC) pathway by responding to increases in uncharged tRNA levels in the cell and causing downregulation of total protein synthesis at the level of initiation. However, these eEF1A mutant strains do not exhibit increased levels of uncharged tRNAs, suggesting an alternate mechanism of Gcn2p activation. Thus, we hypothesize there is interplay between the translation initiation and elongation defects in eEF1A actin bundling mutant strains. The recent finding that Gcn2p and eEF1A directly interact sheds light on this new function. The interactions between Gcn2p and eEF1A actin bundling mutants as well as the specific functions of eEF1A within elongation are being assessed. Support: NIH 5T32AI007403–18