Intrinsic RNA-Binding Preferences of Eukaryotic Translation Initiation Factor eIF4G Contribute to Competitive Discrimination of Different mRNAs. Saccharomyces cerevisiae S288C

Translational control of gene expression plays essential roles in cellular stress responses and organismal development by enabling rapid, selective, and localized control of protein production. Translational regulation depends on context-dependent differences in the translational efficiencies of mRNAs, but the key mRNA features that distinguish efficiently translated mRNAs are largely unknown. Here we comprehensively determined the RNA-binding preferences of the initiation factor eIF4G to assess whether core translation initiation factors have intrinsic sequence preferences that contribute to preferential translation of specific mRNAs. We identified a simple sequence motif—oligo-uridine—that mediates high-affinity binding to eIF4G. Oligo(U) motifs occur naturally in the transcript leaders of hundreds of yeast genes and are conserved between yeast species. Notably, mRNAs containing oligo(U) motifs resist translational repression upon depletion of eIF4G, demonstrating the impact of these motifs in vivo. Together, our data suggest a mechanism for selective translational control mediated by core initiation factors.