| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 34, 31270-31278, August 23, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Department of Biochemistry and Molecular Pharmacology,
School of Medicine, West Virginia University,
Morgantown, West Virginia 26506
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.
Inhibition of the Splicing of Glucose-6-phosphate Dehydrogenase
Precursor mRNA by Polyunsaturated Fatty Acids*
,,
*
This work was supported by National Institutes of Health
Grant DK46897.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
These authors contributed equally to this work.
§
To whom correspondence should be addressed: Dept. of Biochemistry
and Molecular Pharmacology, WVU, Health Sciences Center, P. O. Box
9142, Morgantown, WV 26506. Tel.: 304-293-7759; Fax: 304-293-6846;
E-mail:LSALATI@hsc.wvu.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Wakao, C. Andre, and C. Benning Functional Analyses of Cytosolic Glucose-6-Phosphate Dehydrogenases and Their Contribution to Seed Oil Accumulation in Arabidopsis Plant Physiology, January 1, 2008; 146(1): 277 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Rukov, M. Irimia, S. Mork, V. K. Lund, J. Vinther, and P. Arctander High Qualitative and Quantitative Conservation of Alternative Splicing in Caenorhabditis elegans and Caenorhabditis briggsae Mol. Biol. Evol., April 1, 2007; 24(4): 909 - 917. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Szeszel-Fedorowicz, I. Talukdar, B. N. Griffith, C. M. Walsh, and L. M. Salati An Exonic Splicing Silencer Is Involved in the Regulated Splicing of Glucose 6-Phosphate Dehydrogenase mRNA J. Biol. Chem., November 10, 2006; 281(45): 34146 - 34158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. W. Harries, S. Ellard, A. Stride, The European MODY consortium, N. G. Morgan, and A. T. Hattersley Isomers of the TCF1 gene encoding hepatocyte nuclear factor-1 alpha show differential expression in the pancreas and define the relationship between mutation position and clinical phenotype in monogenic diabetes Hum. Mol. Genet., July 15, 2006; 15(14): 2216 - 2224. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Siculella, S. Sabetta, A. M. Giudetti, and G. V. Gnoni Hypothyroidism Reduces Tricarboxylate Carrier Activity and Expression in Rat Liver Mitochondria by Reducing Nuclear Transcription Rate and Splicing Efficiency J. Biol. Chem., July 14, 2006; 281(28): 19072 - 19080. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Talukdar, W. Szeszel-Fedorowicz, and L. M. Salati Arachidonic Acid Inhibits the Insulin Induction of Glucose-6-phosphate Dehydrogenase via p38 MAP Kinase J. Biol. Chem., December 9, 2005; 280(49): 40660 - 40667. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Salati, W. Szeszel-Fedorowicz, H. Tao, M. A. Gibson, B. Amir-Ahmady, L. P. Stabile, and D. L. Hodge Nutritional Regulation of mRNA Processing J. Nutr., September 1, 2004; 134(9): 2437S - 2443S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Siculella, F. Damiano, S. Sabetta, and G. V. Gnoni n-6 PUFAs downregulate expression of the tricarboxylate carrier in rat liver by transcriptional and posttranscriptional mechanisms J. Lipid Res., July 1, 2004; 45(7): 1333 - 1340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Stamm Signals and their transduction pathways regulating alternative splicing: a new dimension of the human genome Hum. Mol. Genet., October 1, 2002; 11(20): 2409 - 2416. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
