The 3'-untranslated region of ADAMTS1 regulates its mRNA stability

Acta Med Okayama. 2009 Apr;63(2):79-85. doi: 10.18926/AMO/31831.

Abstract

ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an inflammatory-induced gene. We have previously reported that ADAMTS1 was strongly but transiently expressed in the infarcted heart. In this study, we investigated whether a 3'-untranslated region (UTR) affects the mRNA stability of this gene. When stimulated with tissue necrosis factor (TNF)-alpha, the expression level of ADAMTS1 mRNA rapidly increased, but the induction of ADAMTS1 mRNA peaked at 6h after stimulation, after which the expression levels of ADAMTS1 mRNA decreased. The 3'-UTR ADAMTS1 mRNA contains multiple adenine and uridine-rich elements, suggesting that the 3'-UTR may regulate gene stability. The addition of actinomycin D, an RNA synthesis inhibitor, demonstrated the decay of induced ADAMTS1 mRNA by TNF-alpha. Furthermore, a region containing multiple AUUUA motifs within the ADAMTS1 3'-UTR destabilized transfected Enhanced Green Fluorescence Protein (EGFP) mRNA expression. These results demonstrated that the ADAMTS1 3'-UTR may regulate the expression of ADAMTS1 mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics*
  • ADAM Proteins* / genetics
  • ADAM Proteins* / metabolism
  • ADAMTS1 Protein
  • Animals
  • Base Sequence
  • COS Cells
  • Chlorocebus aethiops
  • Dactinomycin / metabolism
  • Humans
  • Mice
  • Molecular Sequence Data
  • Nucleic Acid Synthesis Inhibitors / metabolism
  • RNA Stability / genetics*
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • 3' Untranslated Regions
  • Nucleic Acid Synthesis Inhibitors
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor-alpha
  • Dactinomycin
  • ADAM Proteins
  • ADAMTS1 Protein
  • ADAMTS1 protein, human