Scd6 Targets eIF4G to Repress Translation: RGG Motif Proteins as a Class of eIF4G-Binding Proteins

SummaryThe formation of mRNPs controls the interaction of the translation and degradation machinery with individual mRNAs. The yeast Scd6 protein and its orthologs regulate translation and mRNA degradation in yeast, C. elegans, D. melanogaster, and humans by an unknown mechanism. We demonstrate that Scd6 represses translation by binding the eIF4G subunit of eIF4F in a manner dependent on its RGG domain, thereby forming an mRNP repressed for translation initiation. Strikingly, several other RGG domain-containing proteins in yeast copurify with eIF4E/G and we demonstrate that two such proteins, Npl3 and Sbp1, also directly bind eIF4G and repress translation in a manner dependent on their RGG motifs. These observations identify the mechanism of Scd6 function through its RGG motif and indicate that eIF4G plays an important role as a scaffolding protein for the recruitment of translation repressors.

► Proteins with RGG motifs bind eIF4G and repress translation through their RGG motifs
► Scd6 forms a tricomplex with eIF4E-4G and prevents the recruitment of 43S complex
► eIF4G acts as a scaffold to recruit the RGG motif containing translation repressors
► eIF4G protein functions as an integrator of mRNP fate in an mRNA life cycle