TY - JOUR
T1 - The 3'-untranslated region of ADAMTS1 regulates its mRNA stability
AU - Hatipoglu, Omer Faruk
AU - Hirohata, Satoshi
AU - Yaykasli, Kursat Oguz
AU - Cilek, Mehmet Zeynel
AU - Demircan, Kadir
AU - Shinohata, Ryoko
AU - Yonezawa, Tomoko
AU - Oohashi, Toshitaka
AU - Kusachi, Shozo
AU - Ninomiya, Yoshifumi
PY - 2009/5
Y1 - 2009/5
N2 - ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an inflammatoryinduced 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.
AB - ADAMTS1 (a disintegrin and metalloproteinase with thrombospondin motifs 1) is an inflammatoryinduced 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.
KW - ADAMTS1
KW - Gene regulation
KW - Metalloproteinase
UR - http://www.scopus.com/inward/record.url?scp=65549161760&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65549161760&partnerID=8YFLogxK
M3 - Article
C2 - 19404339
AN - SCOPUS:65549161760
SN - 0386-300X
VL - 63
SP - 79
EP - 85
JO - Acta medica Okayama
JF - Acta medica Okayama
IS - 2
ER -