L'initiation de la traduction chez les eucaryotes, source de diversification et de modulation de l'expression des gènes

Abstract

Recent progress in understanding the translation process in eukaryotes gives a new insight on the mechanisms by which gene expression is modulated. The initiation step of translation plays a key role in this control. Apart from eukaryotic viruses, a growing number of genes encoding regulatory proteins uses translation initiation to increase gene diversity. 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 initiation site by the scanning initiation complex is dependent on the context surrounding the initiator AUG codon. In this article, we describe the cis-acting elements of mRNA which influence translation initiation. A weak context around the AUG codon interferes with recognition of the initiator codon and allows initiation at downstream AUGs. This results 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 are in the same reading frame. This leaky scanning mechanism is also observed when non-AUG codons are used for translation initiation. The regulating elements acting on the scanning of the initiation complexes are secondary structures or translated minicistrons which, in most cases, decrease the translation efficiency at a downstream AUG. As an exception to the scanning model, the mechanism of internal initiation of translation seems to be used to translate some particular mRNA during viral infection or in stress conditions. These elements of translational control allow either the expression of the multiple functions of a gene, or the coordinate regulation of genes involved in the same biochemical pathway. What is more, they permit the fine adjustment of protein synthesis to the variations of cell growth conditions.