A NOVEL INHIBITOR OF CAP-DEPENDENT TRANSLATION INITIATION IN YEAST - P20 COMPETES WITH EIF4G FOR BINDING TO EIF4E

In the yeast Saccharomyces cerevisiae a small protein named p20 is fou nd associated with translation initiation factor eIF4E, the mRNA cap-b inding protein. We demonstrate here that p20 is a repressor of cap-dep endent translation initiation, p20 shows amino acid sequence homology to a region of eIF4G, the large subunit of the cap-binding protein com plex eIF4F, which carries the binding site for eIF4E. Both, eIF4G and p20 bind to eIF4E and compete with each other for binding to eIF4E. Th e eIF4E-p20 complex can bind to the cap structure and inhibit cap-depe ndent but not cap-independent translation initiation: the translation of a mRNA with the 67 nucleotide Omega sequence of tobacco mosaic viru s in its 5' untranslated region (which was previously shown to render translation cap-independent) is not inhibited by p20. Whereas the tran slation of the same mRNA lacking the Omega sequence is strongly inhibi ted by p20. Disruption of CAF20, the gene encoding p20, stimulates the growth of yeast cells, overexpression of p20 causes slower growth of yeast cells. These results show that p20 is a regulator of eIF4E activ ity which represses cap-dependent initiation of translation by interfe ring with the interaction of eIF4E with eIF4G, e.g. the formation of t he eIF4F-complex.