eIF3

eukaryotic initiation factor 3 (eIF3) is a multiprotein complex essential for the initiation of protein synthesis in eukaryotic cells. It operates at an early stage of translation initiation, coordinating assembly of the preinitiation complex and the recruitment of mRNA to the ribosome.

During cap-dependent initiation, eIF3 binds to the 40S ribosomal subunit and interacts with other initiation factors and the eIF4F cap-binding complex. This network helps recruit the 43S preinitiation complex to the mRNA, promotes 5'→3' scanning for the initiator AUG, and stabilizes start codon recognition. The complex also helps prevent premature joining of the 60S subunit, ensuring proper initiation.

Composition and architecture: eIF3 is a large, modular complex comprising multiple subunits. In humans it includes roughly a dozen distinct subunits (commonly referred to as eIF3a through eIF3m, with some letters omitted in certain species). The architecture features a set of PCI-domain–containing subunits and at least one MPN-domain subunit, reflecting its regulatory and scaffolding roles within the initiation machinery.

Regulation and significance: eIF3 participates in broader translational control, responding to cellular signals and stress. Subunits can be regulated by phosphorylation and interaction with other factors, influencing translation efficiency and selectivity. Altered expression or mutation of eIF3 subunits has been linked to cancer and neurodevelopmental disorders, making it a focus of basic and translational research.

Beyond initiation, eIF3 also participates in reinitiation after upstream open reading frame translation and in selective translation of specific mRNAs under stress conditions. Its study continues to reveal how initiation factors coordinate gene expression at the level of translation.