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Activation of transcription of hepatic HMG‐CoA reductase by insulin requires tristetraprolin
Author(s) -
Ness Gene Charles,
Edelman Jeffrey
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.931.1
Subject(s) - transcription (linguistics) , small interfering rna , reductase , transcription factor , tristetraprolin , messenger rna , microbiology and biotechnology , rna interference , chemistry , rna , biology , rna binding protein , biochemistry , enzyme , gene , philosophy , linguistics
As part of a study of the actions of AU‐rich RNA binding proteins, we noted that in vivo electroporation of siRNAs to tristetraprolin (TTP) completed eliminated transcription from wild type HMG‐CoA reductase luciferase construct in normal rats. siRNAs to several other AU‐rich binding proteins had little effect except that two siRNAs to HuR (1 of 4 mammalian homologs of Drosophila embryonic lethal abnormal vision proteins) also decreased transcriptional activity of HMG‐CoA reductase. TTP mRNA is increased within 10 minutes after giving insulin to fibroblasts overexpressing normal human insulin receptors. Since insulin acts within 2 hrs to increase transcription of hepatic HMG‐CoA reductase, we investigated the effect of TTP siRNAs on the insulin stimulation of HMG‐CoA reductase transcription by performing in vivo electroporation experiments. TTP siRNAs eliminated the insulin mediated increase in transcription. In comparison, siRNA to HuR reduced the increase in transcription due to insulin. siRNA to AUH (AU RNA binding protein/enoyl coenzyme A hydratase) had no effect on transcription. TTP is a CCCH tandem zinc finger protein widely known to bind to AU‐rich elements in RNA and cause mRNA degradation. This study demonstrates that TTP also participates in activation of transcription of hepatic HMG‐CoA reductase in vivo. (Supported by research grant R01 DK 075414.)