S-Space College of Natural Sciences (자연과학대학) Dept. of Biological Sciences (생명과학부) Journal Papers (저널논문_생명과학부)
Regulation of ApC/EBP mRNA by the Aplysia AU-rich element-binding protein, ApELAV, and its effects on 5-hydroxytryptamine-induced long-term facilitation
- Yim, Se‐Jeong; Lee, Yong‐Seok; Lee, Jin‐A; Chang, Deok‐Jin; Han, Jin‐Hee; Kim, Hyoung; Park, Hyungju; Jun, Heejung; Kim, V. Narry; Kaang, Bong‐Kiun
- Issue Date
- Journal of Neurochemistry, Vol.98 No.2, pp.420-429
- CCAAT enhancer-binding protein; Aplysia; AU-rich element (ARE)-binding protein; long-term facilitation; memory; synaptic plasticity
- 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.
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