Regulation of ApC/EBP mRNA by the Aplysia AU-rich element-binding protein, ApELAV, and its effects on 5-hydroxytryptamine-induced long-term facilitation.
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.
Yim
Se-Jeong
SJ
National Research Laboratory, Institute of Molecular Biology and Genetics, School of Biological Sciences, College of Natural Sciences, Seoul National University, San 56-1 Silim-dong, Gwanak-gu, Seoul 151-747, Korea.
Lee
Yong-Seok
YS
Lee
Jin-A
JA
Chang
Deok-Jin
DJ
Han
Jin-Hee
JH
Kim
Hyoung
H
Park
Hyungju
H
Jun
Heejung
H
Kim
V Narry
VN
Kaang
Bong-Kiun
BK
D020413:3' Untranslated Regions / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter / Q000235:genetics; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism*; D017403:In Situ Hybridization; D017774:Long-Term Potentiation / Q000187:drug effects*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology
D020413:3' Untranslated Regions; D022762:CCAAT-Enhancer-Binding Proteins; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012701:Serotonin; D008156:Luciferases