eIF3: a critical player in mRNA recruitment to the ribosome with emerging roles across translation

Eukaryotic translation initiation factor (eIF) 3 is a multi-subunit protein complex that plays critical roles throughout translation initiation and has been implicated in a variety of human diseases. More recently, eIF3 has been tied to translation elongation and termination, as well as translational regulation. And yet, a mechanistic understanding of how eIF3 and its constituent subunits perform their canonical roles during initiation continues to elude us. Work across the last two decades has delineated broad mechanistic roles for some of these subunits and identified distinct modules of the complex that contribute differentially to the recruitment of messenger RNA (mRNA) to the ribosome during initiation. Structural approaches have further illuminated these putative roles. And yet, key mechanistic questions tied to fundamental technical challenges remain. Even so, new developments are poised to address these challenges and push our understanding of eIF3 function forward in the coming years.