INITIATION OF TRANSLATION IN EUKARYOTES - DIVERSITY AND MODULATION OFGENE-EXPRESSION

Recent progress in understanding the translation process in eukaryotes gives a new insight on the mechanisms by which gene expression is mod ulated. The initiation step of translation plays a key role in this co ntrol. Apart from eukaryotic viruses, a growing number of genes encodi ng regulatory proteins uses translation initiation to increase gene di versity. The scanning model of Kozak describes the mechanism by which the 40S ribosomal subunit enters at the capped 5' end of the messenger RNA and scans to the first initiator codon. Recognition of the initia tion site by the scanning initiation complex is dependent on the conte xt surrounding the initiator AUG codon. In this article, we describe t he cis-acting elements of mRNA which influence translation initiation. A weak context around the AUG codon interferes with recognition of th e initiator codon and allows initiation at downstream AUGs. This resul ts either in the expression of two genes on a bicistronic mRNA, or in the synthesis of several forms of a protein if the initiator codons ar e in the same reading frame. This leaky scanning mechanism is also obs erved when non-AUG codons are used for translation initiation. The reg ulating elements acting on the scanning of the initiation complexes ar e secondary structures or translated minicistrons which, in most cases , decrease the translation efficiency at a downstream AUG. As an excep tion to the scanning model, the mechanism of internal initiation of tr anslation seems to be used to translate some particular mRNA during vi ral infection or in stress conditions. These elements of translational control allow either the expression of the multiple functions of a ge ne, or the coordinate regulation of genes involved in the same biochem ical pathway. What is more, they permit the fine adjustment of protein synthesis to the variations of cell growth conditions.