Inhibition of the splicing of glucose-6-phosphate dehydrogenase precursor mRNA by polyunsaturated fatty acids.
نویسندگان
چکیده
Polyunsaturated fatty acids inhibit the expression of hepatic glucose-6-phosphate dehydrogenase (G6PD) by changes in the amount of G6PD pre-mRNA in the nucleus in the absence of changes in the transcription rate of the gene. We have compared the nuclear accumulation of partially and fully spliced mRNA for G6PD in the livers of mice fed diets high versus low in polyunsaturated fat. Consumption of a diet high in polyunsaturated fat decreased the accumulation of partially spliced forms of the G6PD pre-mRNA. Examining the fate of multiple introns within the G6PD primary transcript indicated that in mice fed a high fat diet, G6PD pre-mRNA containing intron 11 accumulated within the nucleus, whereas G6PD mature mRNA abundance was inhibited 50% or more within the same livers. Transient transfection of RNA reporters into primary hepatocyte cultures was used to localize the cis-acting RNA element involved in this regulated splicing. Reporter RNA produced from constructs containing exon 12 were decreased in amount by arachidonic acid. The extent of this decrease paralleled that seen in the expression of the endogenous G6PD mRNA. The presence of both exon 12 and a neighboring intron within the G6PD reporter RNA was essential for regulation by polyunsaturated fatty acid. Inhibition was not dependent on the presence of the G6PD polyadenylation signal and the 3'-untranslated region, but substitution with the SV40 poly(A) signal attenuated the inhibition by arachidonic acid. Thus, exon 12 contains a putative splicing regulatory element involved in the inhibition of G6PD expression by polyunsaturated fat.
منابع مشابه
Polyunsaturated fatty acids inhibit the expression of the glucose-6-phosphate dehydrogenase gene in primary rat hepatocytes by a nuclear posttranscriptional mechanism.
Expression of the glucose-6-phosphate dehydrogenase (G6PD) gene is inhibited by the addition of polyunsaturated fatty acids to the medium of primary hepatocytes in culture. To define the regulated step, we measured the abundance of G6PD mRNA both in the nucleus and in total RNA and measured the transcriptional activity of the G6PD gene. Insulin and glucose stimulated a 5- to 7-fold increase in ...
متن کاملInhibition of Human Erythrocyte Glucose 6-Phosphate Dehydrogenase by Cadmium, Nickel and Aluminium
متن کامل
INHIBITION OF HUMAN ERYTHROCYTE GLUCOSE 6-PHOSPHATE DEHYDROGENASE ACTIVITY BY DEHYDROEPIANDROSTERONE AND RELATED STEROIDS.
The inhibitory effects of several steroids on G6PD activity using intact erythrocytes are reported. Incubation of whole blood with dehydroepiandrosterone (DHEA) resulted in 42% and 12% inhibition in the enzyme activity in the presence and absence of oxygen, respectively. Addition of epinephrine and/or aminophylline into the incubation medium caused further enzyme inhibition suggesting a po...
متن کاملProtective role of glucose-6-phosphate dehydrogenase activity in the metabolic response of C6 rat glioma cells to polyunsaturated fatty acid exposure.
Polyunsaturated fatty acids (PUFAs) can influence tumor growth and migration, both in vitro and in vivo. The PUFA gamma-linolenic acid (GLA) has been reported to improve the poor prognosis associated with human gliomas, although its effects at sublethal concentrations on residual cells postsurgery are poorly understood. The study investigated the effects sublethal PUFA doses (90 or 150 microM) ...
متن کاملArachidonic acid inhibits the insulin induction of glucose-6-phosphate dehydrogenase via p38 MAP kinase.
Polyunsaturated fatty acids are potent inhibitors of lipogenic gene expression in liver. The lipogenic enzyme glucose-6-phosphate dehydrogenase (G6PD) is unique in this gene family, in that fatty acids inhibit at a post-transcriptional step. In this study, we have provided evidence for a signaling pathway for the arachidonic acid inhibition of G6PD mRNA abundance. Arachidonic acid decreases the...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- The Journal of biological chemistry
دوره 277 34 شماره
صفحات -
تاریخ انتشار 2002