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.
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 17 beta-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 nuclear-localized 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.
Arao
Yukitomo
Y
Department of Environmental Medicine, Center for Community Medicine, Jichi Medical School, Tochigi 329-0498, Japan. ya@jichi.ac.jp.
Kikuchi
Atsumi
A
Kishida
Mitsuyo
M
Yonekura
Masami
M
Inoue
Akira
A
Yasuda
Shigemitsu
S
Wada
Seiki
S
Ikeda
Kazuhiro
K
Kayama
Fujio
F
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology* / Q000502:physiology; D005260:Female; D006367:HeLa Cells; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000032:analysis* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D020871:RNA Stability; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014599:Uterus / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*
D020413:3' Untranslated Regions; D004967:Estrogens; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630988:Hnrnpd protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins