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Supplement: Nutrition and Gene Regulation

Nutritional Regulation of mRNA Processing^1,2

Department of Biochemistry and Molecular Pharmacology, School of Medicine, West Virginia University, Morgantown, WV

³To whom correspondence should be addressed. E-mail: Lsalati{at}hsc.wvu.edu.

Understanding how a cell adapts to dietary energy in the form of carbohydrate versus energy in the form of triacylglycerol requires knowledge of how the activity of the enzymes involved in lipogenesis is regulated. Changes in the activity of these enzymes are largely caused by changes in the rate at which their proteins are synthesized. Nutrients within the diet can signal these changes either via altering hormone concentrations or via their own unique signal transduction pathways. Most of the lipogenic genes are regulated by changes in the rate of their transcription. Glucose-6-phosphate dehydrogenase (G6PD) is unique in this group of enzymes in that nutritional regulation of its synthesis involves steps exclusively at a posttranscriptional level. G6PD activity is enhanced by the consumption of diets high in carbohydrate and is inhibited by the consumption of polyunsaturated fat. In this review, evidence is presented that changes in the rate of synthesis of the mature G6PD mRNA involves regulation of the efficiency of splicing of the nascent G6PD transcript. Furthermore, this regulation involves the activity of a cis-acting sequence in the G6PD primary transcript. This sequence in exon 12 is essential for the inhibition of G6PD mRNA splicing by PUFA. Understanding the mechanisms by which nutrients alter nuclear posttranscriptional events will provide new information on the breadth of mechanisms involved in gene regulation.

KEY WORDS: • RNA splicing • posttranscriptional • gene expression • polyunsaturated fat

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