Whole-proteome profiling enabled us to compare proteomic differences between a Saccharomyces cerevisiae parental strain (PIC2-GFP) and two derived mutants lacking Nab3 RNA-binding sites in PIC2. Previous experiments had established that disrupting Nab3 binding to PIC2 while maintaining Nrd1 binding to the same transcript led to severe growth defects, larger cell size, delayed cell cycle and resistance to oxidative stress. Following characterization of a PIC2-overexpressing mutant we established that these phenotypes were not related to Pic2 overabundance. Therefore, the purpose of this experiment was to determine (i) whether the proteomic signature of the mutant lacking Nab3 RNA-binding sites in PIC2 could account for the observed phenotypes and (ii) if the proteins that were differentially expressed in such mutant were targeted by Nab3 and Nrd1.