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Stability of A+U-Rich Element Binding Factor 1 (AUF1)-Binding Messenger Ribonucleic Acid Correlates with the Subcellular Relocalization of AUF1 in the Rat Uterus upon Estrogen Treatment

Department of Environmental Medicine (Y.A., A.K., M.K., S.Y., K.I., F.K.), Center for Community Medicine, Jichi Medical School, Tochigi 329-0498; School of Agriculture (M.K., M.Y.), Ibaraki University, Ibaraki 300-0393; Graduate School of Medicine (A.I.), Osaka City University, Osaka 545-8585; Fourth Department of Internal Medicine (S.Y., S.W.), Saitama Medical School, Saitama 350-0495; and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Saitama 332-0012, Japan

Address all correspondence and requests for reprints to: Yukitomo Arao, Department of Environmental Medicine, Center for Community Medicine, Jichi Medical School, Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi 329-0498, Japan. E-mail: ya{at}jichi.ac.jp.

The nucleocytoplasmic shuttling protein, A+U-rich element binding factor 1 (AUF1), is one of the RNA-binding proteins that specifically bind adenylate-uridylate rich elements (AREs) in mRNA 3'-untranslated regions (UTRs), and acts as a regulator of ARE-mediated mRNA degradation in the cytoplasm. We previously reported that in the female rat uterus, the levels of specific AUF1 isoform mRNAs (p40/p45) were increased by 17ß-estradiol (E2) treatment. Therefore, we examined the role of AUF1 in the regulation of E2-mediated mRNA turnover in the rat uterus. We identified ABIN2 and Ier2/pip92 mRNAs as candidate targets of AUF1 in the rat uterus. We found that AUF1-binding elements were present in the 3'-UTR of both mRNAs and that the 3'-UTRs functioned as mRNA turnover regulatory elements. In the ovariectomized rat uterus, the nucleocytoplasmic localization of AUF1p40/p37 isoform proteins was regulated by E2. We also found that cytoplasmic AUF1-bound mRNA levels changed coincidentally with the cytoplasmic levels of AUF1p40/p37. Finally, we confirmed that the subcellular localization of AUF1p40 controlled the stability of target mRNAs in vitro, such that cytoplasmically localized AUF1p40 led to marked mRNA stabilization, whereas nuclearlocalized AUF1p40 stabilized target mRNA only slightly. These results suggested that E2-inducible ARE-containing gene transcripts are regulated, at least in part, via mRNA stabilization through the nucleocytoplasmic relocalization of AUF1.

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Ligands:   17β-Estradiol

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