Kuželov seminár

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.