title: The 3'-untranslated region of ADAMTS1 regulates its mRNA stability.
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.
authors.affiliation: Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8530, Japan.
authors.forename: Omer Faruk
authors.initials: OF
authors.lastname: Hatipoglu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirohata
authors.forename: Kursat Oguz
authors.initials: KO
authors.lastname: Yaykasli
authors.forename: Mehmet Zeynel
authors.initials: MZ
authors.lastname: Cilek
authors.forename: Kadir
authors.initials: K
authors.lastname: Demircan
authors.forename: Ryoko
authors.initials: R
authors.lastname: Shinohata
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yonezawa
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Oohashi
authors.forename: Shozo
authors.initials: S
authors.lastname: Kusachi
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ninomiya
mesh_terms: 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
chemical_list: 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