Polyunsaturated Fatty Acids Suppress Hepatic Sterol Regulatory Element-binding Protein-1 Expression by Accelerating Transcript Decay

Jing Xu, Margarita Teran-Garcia, Jung H.Y. Park, Manabu T. Nakamura, Steven D. Clarke

Research output: Contribution to journalArticlepeer-review

Abstract

The reduction in hepatic abundance of sterol regulatory element binding protein-1 (SREBP-1) mRNA and protein associated with the ingestion of polyunsaturated fatty acids (PUFA) appears to be largely responsible for the PUFA-dependent inhibition of lipogenic gene transcription. Our initial studies indicated that the induction of SREBP-1 expression by insulin and glucose was blocked by PUFA. Nuclear run-on assays suggested PUFA reduced SREBP-1 mRNA by post-transcriptional mechanisms. In this report we demonstrate that PUFA enhance the decay of both SREBP-1a and -1c. When rat hepatocytes in monolayer culture were treated with albumin-bound 20:4(n-6) or 20:5(n-3) the half-life of total SREBP-1 mRNA was reduced by 50%. Ribonuclease protection assays revealed that the decay of SREBP-1c mRNA was more sensitive to PUFA than was SREBP-1a, i.e. the half-life of SREBP-1c and -1a was reduced from 10.0 to 4.6 h and 11.6 to 7.6 h, respectively. Interestingly, treating the hepatocytes with the translational inhibitor, cycloheximide, prevented the PUFA-dependent decay of SREBP-1. This suggests that SREBP-1 mRNA may need to undergo translation to enter the decay process, or that the decay process requires the synthesis of a rapidly turning over protein. Although the mechanism by which PUFA accelerate SREBP-1 mRNA decay remains to be determined, cloning and sequencing of the 3′-untranslated region for the rat SREBP-1 transcript revealed the presence of an A-U-rich region that is characteristic of a destablizing element.

Original languageEnglish (US)
Pages (from-to)9800-9807
Number of pages8
JournalJournal of Biological Chemistry
Volume276
Issue number13
DOIs
StatePublished - Mar 30 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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