Bigger than Expected: IRES-Dependent mRNA Translation Initiation Enlarges the Eukaryotic Proteome

Until recently it was believed that in eukaryotic cells, mRNA translation initiates entirely by binding of the mRNA 5′- m7G cap-structure to the cap-binding complex E1F4F. Anyway, new evidences pointed out that eukaryiotic cells have evolved also alternative translation initiation strategies from one single mRNA, i.e. IRES-dependent mRNA translation initiation, that can increase the size and function of a given cell proteome. Here we briefly discuss the emerging role of protein isoforms deriving from IRES-dependent translation initiation in mammalian cells, at the light of more recent findings.