The 3'-untranslated region of ADAMTS1 regulates its mRNA stability.
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.
Hatipoglu
Omer Faruk
OF
Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8530, Japan.
Hirohata
Satoshi
S
Yaykasli
Kursat Oguz
KO
Cilek
Mehmet Zeynel
MZ
Demircan
Kadir
K
Shinohata
Ryoko
R
Yonezawa
Tomoko
T
Oohashi
Toshitaka
T
Kusachi
Shozo
S
Ninomiya
Yoshifumi
Y
D020413:3' Untranslated Regions / Q000235:genetics*; D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000071097:ADAMTS1 Protein; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002522:Chlorocebus aethiops; D003609:Dactinomycin / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D019384:Nucleic Acid Synthesis Inhibitors / Q000378:metabolism; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D020413:3' Untranslated Regions; D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D051722:ADAM Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human