Thu 28 Apr. 2011, 14:00
Title: eIF3 rocks: From initiation to termination and back to reinitiation
Speaker: Leoš Valášek, Mirkobiologický ústav AV ČR
The initiation of translation in eukaryotes requires the coordinated action of at least 12 eukaryotic initiation factors (eIFs). Among them, eIF3 deserves a special attention owing to a broad range of functions that it is believed to promote. Our research aims at addressing molecular details of the key roles that eIF3 performs in close co-operation with other eIFs not only in general translation initiation, but possibly also in termination and recycling, as well as in the gene-specific regulatory mechanism called reinitiation. In the first part of the lecture I will present our most recent data implicating this bona fide initiation factor in the regulatory events monitoring the fidelity and timing of termination and ribosomal recycling. Unlike in bacteria, where a specific ribosomal recycling factor exists, this last phase of protein synthesis in eukaryotes has remained a true mystery until a couple years ago, when ABCE1/RLI1 and eIF1, eIF1A and eIF3 were proposed to drive this process, at least in in vitro reconstituted translational systems. Our genetic as well as biochemical data now provide important in vivo evidence for the role of eIF3 in termination and suggest a possible mechanism of its involvement. Proper termination followed by incomplete ribosomal recycling, where only the large 60S subunit becomes expelled from the mRNA, represents the critical requirement for one of the most intriguing translational control mechani sms reinitiation. In the second part of my talk, I will demonstrate the key importance of eIF3 also in this process, which is based on the ability of the post - termination small ribosomal subunit to resume scanning after translating a short upstream open reading frame (uORF) in order to be able to reinitiate at a downstream main ORF. Hence eIF3 forms a molecular bridge across several phases of translation indicating that their mutual "communication" and co-ordination arising from it is a lot broader than initially anticipated.