Regulatory signals in messenger RNA: determinants of nutrient-gene interaction and metabolic compartmentation

Nutrition has marked influences on gene expression and an understanding of the interaction between nutrients and gene expression is important in order to provide a basis-for determining the nutritional requirements on an individual basis. The effects of nutrition can be exerted at many stages between transcription of the genetic sequence and production of a functional protein. This review focuses on the role of post-transcriptional control, particularly mRNA stability, translation and localization, in the interactions of nutrients with gene expression. The effects of both macronutrients and micronutrients on regulation of gene expression by post-transcriptional mechanisms are presented and the post-transcriptional regulation of specific genes of nutritional relevance (glucose transporters, transferrin, selenoenzymes, metallothionein, lipoproteins) is described in detail. The function of the regulatory signals in the untranslated regions of the mRNA is highlighted in relation to control of mRNA stability, translation and localization and the importance of these mRNA regions to regulation by nutrients is illustrated by reference to specific examples. The localization of mRNA by signals in the untranslated regions and its function in the spatial organization of protein synthesis is described; the potential of such mechanisms to play a key part in nutrient channelling and metabolic compartmentation is discussed. It is concluded that nutrients can influence gene expression through control of the regulatory signals in these untranslated regions and that the post-transcriptional regulation of gene expression by these mechanisms may influence nutritional requirements. It is emphasized that in studies of nutritional control of gene expression it is important not to focus only on regulation through gene promoters but also to consider the possibility of post-transcriptional control.