The phosphorylation state of eucaryotic initiation factor 2 alters translational efficiency of specific mRNAs.
Phosphorylation of the alpha subunit of the eucaryotic translation initiation factor (eIF-2 alpha) by the double-stranded RNA-activated inhibitor (DAI) kinase correlates with inhibition of translation initiation. The importance of eIF-2 alpha phosphorylation in regulating translation was studied by expression of specific mutants of eIF-2 alpha in COS-1 cells. DNA transfection of certain plasmids could activate DAI kinase and result in poor translation of plasmid-derived mRNAs. In these cases, translation of the plasmid-derived mRNAs was improved by the presence of DAI kinase inhibitors or by the presence of a nonphosphorylatable mutant (serine to alanine) of eIF-2 alpha. The improved translation mediated by expression of the nonphosphorylatable eIF-2 alpha mutant was specific to plasmid-derived mRNA and did not affect global mRNA translation. Expression of a serine-to-aspartic acid mutant eIF-2 alpha, created to mimic the phosphorylated serine, inhibited translation of the mRNAs derived from the transfected plasmid. These results substantiate the hypothesis that DAI kinase activation reduces translation initiation through phosphorylation of eIF-2 alpha and reinforce the importance of phosphorylation of eIF-2 alpha as a way to control initiation of translation in intact cells.
Kaufman
R J
RJ
Genetics Institute, Cambridge, Massachusetts 02140.
Davies
M V
MV
Pathak
V K
VK
Hershey
J W
JW
D000595:Amino Acid Sequence; D001483:Base Sequence; D015342:DNA Probes; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics*; D019892:eIF-2 Kinase
D015342:DNA Probes; D015852:Eukaryotic Initiation Factor-2; D010448:Peptide Initiation Factors; D011506:Proteins; D012333:RNA, Messenger; D011494:Protein Kinases; D019892:eIF-2 Kinase