THE 39-KILODALTON SUBUNIT OF EUKARYOTIC TRANSLATION INITIATION-FACTOR-3 IS ESSENTIAL FOR THE COMPLEXS INTEGRITY AND FOR CELL VIABILITY IN SACCHAROMYCES-CEREVISIAE

Eukaryotic translation initiation factor 3 (eIF3) in the yeast Sacchar omyces cerevisiae comprises about eight polypeptides and plays a centr al role in the binding of methionyl-tRNA, and mRNA to the 40S ribosoma l subunit, The fourth largest subunit, eIF3-p39, was gel purified, and a 12-amino-acid tryptic peptide was sequenced, enabling the cloning o f the TIF34 gene, TIF34 encodes a 38,753-Da protein that corresponds t o eIF3-p39 in size and antigenicity, Disruption of TIF34 is lethal, an d depletion of eIF3-p39 by glucose repression of TIF34 expressed from a GAL promoter results in cessation of cell growth. AS eIF3-p39 levels fall, polysomes become smaller, indicating a role for eIF3-p39 in the initiation phase of protein synthesis, Unexpectedly, depletion result s in degradation of all of the subunit proteins of eIF3 at a rate much faster than the normal turnover rates of these proteins, eIF3-p39 has 46% sequence identity with the p36 subunit of human eIF3, Both protei ns are members of the WD-repeat family of proteins, possessing five to seven repeat elements, Taken together, the results indicate that eIF3 -p39 plays an important, although not necessarily direct, role in the initiation phase of protein synthesis and suggest that it may be requi red for the assembly and maintenance of the eIF3 complex in eukaryotic cells.