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. The proposed research aims at addressing molecular details of several of the key roles that eIF3 performs in close co-operation with other eIFs in general translation initiation and perhaps even beyond that, as well as in the gene-specific regulatory mechan ism called reinitiation. Proposed experiments will be performed using the model organism of budding yeast S. cerevisiae, and the main goals of this proposal include: 1) to elucidate molecular nature of the reinitiation mechanism in yeast and the roles of the N-terminal domain of yeIF3a/TIF32 and ribosomal protein RPS0A in it; 2) to determine factor-requirements for and molecular mechanics of a) mRNA recruitment to the 43S pre-initiation complex and b) subsequent scanning for AUG in vivo; 3) t o investigate whether eIF3 and other eIFs influence termination and promote ribosomal recycling in vivo; 4) to explore a molecular mechanism of the yeIF3c/NIP1 involvement in AUG recognition with respect to its interaction with eIF1; 5) to determine a position of eIF5 on the 40S ribosome.