title: Selenium regulation of the selenoprotein and nonselenoprotein transcriptomes in rodents.
abstract: This review discusses progress in understanding the hierarchy of selenoprotein expression at the transcriptome level from selenium (Se) deficiency to Se toxicity. Microarray studies of the full selenoproteome have found that 5 of 24 rodent selenoprotein mRNA decrease to <40% of Se adequate levels in Se deficient liver but that the majority of selenoprotein mRNA are not regulated by Se deficiency. These differences match with the hierarchy of selenoprotein expression, helping to explain these differences and also showing that selenoprotein transcripts can be used as molecular biomarkers for assessing Se status. The similarity of the response curves for regulated selenoproteins suggests one underlying mechanism is responsible for the downregulation of selenoprotein mRNA in Se deficiency, but the heterogeneity of the UGA position in regulated and nonregulated selenoprotein transcripts now indicates that current nonsense mediated decay models cannot explain which transcripts are susceptible to mRNA decay. Microarray studies on the full liver transcriptome in rats found only <10 transcripts/treatment were significantly down- or upregulated by Se deficiency or by supernutritional Se up to 2.0 μg Se/g diet (20× requirement), suggesting that cancer prevention associated with supernutritional Se may not be mediated by transcriptional changes. Toxic dietary Se at 50× requirement (5 μg Se/g diet), however, significantly altered ∼4% of the transcriptome, suggesting number of transcriptional changes itself as a biomarker of Se toxicity. Finally, panels of Se regulated selenoprotein plus nonselenoprotein transcripts predict Se status from deficient to toxic better than conventional biomarkers, illustrating potential roles for molecular biomarkers in nutrition.
authors.affiliation: Department of Nutritional Sciences, University of Wisconsin, Madison, WI 53706, USA. sunde@nutrisci.wisc.edu.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Sunde
authors.forename: Anna M
authors.initials: AM
authors.lastname: Raines
mesh_terms: D000818:Animals; D004032:Diet; D005260:Female; D008099:Liver / Q000378:metabolism; D008297:Male; D046228:Microarray Analysis; D009752:Nutritional Status; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D012643:Selenium / Q000172:deficiency / Q000378:metabolism* / Q000506:poisoning; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D012333:RNA, Messenger; D051140:Selenoproteins; D012643:Selenium