Protein Synthesis in Eukaryotes: Internal Initiation

Abstract Internal initiation is an alternative mechanism to the general pathway of translation initiation in eukaryotes and involves the internal binding of ribosomes to a specific sequence in the messenger ribonucleic acid (mRNA) called the internal ribosome entry site (IRES). The mRNA 5′ cap structure and a cap‐binding protein, eukaryotic initiation factor (eIF) 4E, play a key role in the canonical mechanism of translation initiation. However, internal initiation is independent of the cap structure and eIF4E. IRES‐mediated translation initiation has been documented for viral and cellular mRNAs, and functions during mitosis and stress conditions, such as apoptosis and hypoxia.