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

• Published in: Molecular endocrinology (Baltimore, Md.) Vol. 18; no. 9; pp. 2255 - 2267
• Main Authors: Arao, Yukitomo, Kikuchi, Atsumi, Kishida, Mitsuyo, Yonekura, Masami, Inoue, Akira, Yasuda, Shigemitsu, Wada, Seiki, Ikeda, Kazuhiro, Kayama, Fujio
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01-09-2004; Oxford University Press
• Subjects: 3' Untranslated Regions - genetics; 3' Untranslated Regions - metabolism; Animals; Base Sequence; Cell Nucleus - chemistry; Cell Nucleus - metabolism; Cytoplasm - chemistry; Cytoplasm - metabolism; Estrogens - pharmacology; Estrogens - physiology; Female; HeLa Cells; Heterogeneous Nuclear Ribonucleoprotein D0; Heterogeneous-Nuclear Ribonucleoprotein D - analysis; Heterogeneous-Nuclear Ribonucleoprotein D - genetics; Heterogeneous-Nuclear Ribonucleoprotein D - metabolism; Humans; Molecular Sequence Data; Rats; RNA Stability; RNA, Messenger - analysis; RNA, Messenger - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Uterus - chemistry; Uterus - cytology; Uterus - metabolism
• ISSN: 0888-8809; 1944-9917
• DOI: 10.1210/me.2004-0103

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 17β-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.