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Regulation of ApC/EBP mRNA by the Aplysia AU‐rich element‐binding protein, ApELAV, and its effects on 5‐hydroxytryptamine‐induced long‐term facilitation
Author(s) -
Yim SeJeong,
Lee YongSeok,
Lee JinA,
Chang DeokJin,
Han JinHee,
Kim Hyoung,
Park Hyungju,
Jun Heejung,
Kim V. Narry,
Kaang BongKiun
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03887.x
Subject(s) - aplysia , biology , messenger rna , untranslated region , three prime untranslated region , rna binding protein , microbiology and biotechnology , gene expression , regulation of gene expression , gene , biochemistry , neuroscience
Aplysia CCAAT enhancer‐binding protein (ApC/EBP), a key molecular switch in 5‐hydroxytryptamine (5‐HT)‐induced long‐term facilitation of Aplysia , is quickly and transiently expressed in response to a 5‐HT stimulus, but the mechanism underlying this dynamic expression profile remains obscure. Here, we report that the dynamic expression of ApC/EBP during long‐term facilitation is regulated at the post‐transcriptional level by AU‐rich element (ARE)‐binding proteins. We found that the 3′UTR of ApC/EBP mRNA contains putative sequences for ARE, which is a representative post‐transcriptional cis ‐acting regulatory element that modulates the stability and/or the translatability of a distinct subset of labile mRNAs. We cloned the Aplysia homologue of embryonic lethal abnormal visual system homologue (ELAV/Hu) protein, one of the best‐studied RNA‐binding proteins that associate with ARE, and elucidated the involvement of Aplysia ELAV/Hu protein in ApC/EBP gene expressional regulation. Cloned Aplysia ELAV/Hu protein, Aplysia embryonic lethal abnormal visual system (ApELAV), bound to an AU‐rich region within the 3′UTR of ApC/EBP mRNA. Additionally, ApELAV controlled the expression of ApC/EBP 3′UTR‐containing reporter gene by functioning as a stability‐enhancing factor. In particular, 5‐HT‐induced long‐term facilitation was impaired when the AU‐rich region within the 3′UTR of ApC/EBP was over‐expressed, which suggests the significance of this region in 5‐HT‐induced ApC/EBP expression, and in the resultant formation of long‐term facilitation. Our results imply that the Aplysia ARE‐binding protein, ApELAV, can regulate ApC/EBP gene expression at the mRNA level, and accordingly, ARE‐mediated post‐transcriptional mechanism may serve a crucial function in regulating the expression of ApC/EBP in response to a 5‐HT stimulus.