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J. Biol. Chem., Vol. 268, Issue 18, 13748-13755, 06, 1993
JA Chiorini, TR Boal, S Miyamoto and B Safer
Eukaryotic translation initiation factor 2 (eIF-2) is a heterotrimer
composed of three subunits designated alpha, beta, and gamma. These
proteins exist in equimolar amounts in the cell and have not been detected
as isolated subunits. Our research examines the basis of their balanced
synthesis. Northern analysis of K562 cell mRNA revealed that eIF-2 beta was
five times more abundant than eIF-2 alpha. However, immunoprecipitation of
pulse-labeled K562 cells showed an equimolar rate of synthesis of eIF-2
alpha and -beta despite the 5-fold difference in the size of their mRNA
pools. Addition of equal amounts of synthetic capped mRNA for eIF-2 alpha
and eIF-2 beta to an in vitro translation reaction produced five times more
eIF-2 alpha protein than eIF-2 beta. Determination of the polysome profile
for alpha and beta mRNA in K562 cells indicated eIF-2 alpha was translated
more efficiently than eIF-2 beta. Substitution of either the initiation
codon context or the leader of the beta mRNA for that of alpha had only a
minor effect on the translational efficiency of beta. Comparison of the
rate of ribosomal elongation for the two mRNAs indicated that ribosomes
associated with the beta mRNA elongate at a rate 4-fold less than that of
eIF-2 alpha. Thus, the balanced translation of alpha and beta mRNA is
primarily the result of a 4-fold difference in the rate of ribosomal
elongation.
A difference in the rate of ribosomal elongation balances the synthesis of eukaryotic translation initiation factor (eIF)-2 alpha and eIF-2 beta
Section on RNA and Protein Biosynthesis, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
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J. A. Chiorini, S. Miyamoto, S. J. Harkin, and B. Safer Genomic Cloning and Characterization of the Human Eukaryotic Initiation Factor-2beta Promoter J. Biol. Chem., February 12, 1999; 274(7): 4195 - 4201. [Abstract] [Full Text] [PDF] |
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