title: Intracellular trafficking of micronutrients: from gene regulation to nutrient requirements.
abstract: The intracellular distribution of micronutrients, as well as their uptake, is important for cell function. In some cases the distribution of micronutrients or their related proteins is determined by gene expression mechanisms. The 3' untranslated region (3'UTR) of metallothionein-1 mRNA determines localisation of the mRNA, and in turn intracellular trafficking of the protein product. Using transfected cells we have evidence for the trafficking of metallothionein-1 into the nucleus and for its involvement in protection from oxidative stress and DNA damage. When nutritional supply of Se is limited, selenoprotein expression is altered, but not all selenoproteins are affected equally; the available Se is prioritised for synthesis of particular selenoproteins. The prioritisation involves differences in mRNA translation and stability due to 3'UTR sequences. Potentially, genetic variation in these regulatory mechanisms may affect nutrient requirements. Genetic polymorphisms in the 3'UTR from two selenoprotein genes have been observed; one polymorphism affects selenoprotein synthesis. These examples illustrate how molecular approaches can contribute at several levels to an increased understanding of nutrient metabolism and requirements. First, they provide the tools to investigate regulatory features in genes and their products. Second, understanding these processes can provide model systems to investigate nutrient metabolism at the cellular level. Third, once key features have been identified, the availability of human genome sequence information and single nucleotide polymorphism databases present possibilities to define the extent of genetic variation in genes of nutritional relevance. Ultimately, the functionality of any variations can be defined and subgroups of the population with subtly different nutrient requirements identified.
authors.affiliation: Department of Biological and Nutritional Sciences, University of Newcastle, Newcastle-upon-Tyne NE1 7RU, UK. J.E.Hesketh@ncl.ac.uk
authors.forename: John E
authors.initials: JE
authors.lastname: Hesketh
authors.forename: Stéphane
authors.initials: S
authors.lastname: Villette
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D018977:Micronutrients / Q000378:metabolism*; D009751:Nutritional Requirements; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012643:Selenium / Q000378:metabolism; D051140:Selenoproteins; D014162:Transfection
chemical_list: D018977:Micronutrients; D011506:Proteins; D012333:RNA, Messenger; D051140:Selenoproteins; D008668:Metallothionein; D012643:Selenium