Regulation of ApC/EBP mRNA by the Aplysia AU-rich element-binding protein, ApELAV, and its effects on 5-hydroxytryptamine-induced long-term facilitation

J Neurochem. 2006 Jul;98(2):420-9. doi: 10.1111/j.1471-4159.2006.03887.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / metabolism
  • Amino Acid Sequence
  • Animals
  • Aplysia / metabolism*
  • CCAAT-Enhancer-Binding Proteins / biosynthesis*
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • Cells, Cultured
  • Cloning, Molecular
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Regulation / drug effects
  • Genes, Reporter / genetics
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D / metabolism*
  • In Situ Hybridization
  • Long-Term Potentiation / drug effects*
  • Luciferases / genetics
  • Luciferases / metabolism
  • Molecular Sequence Data
  • Protein Binding
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / isolation & purification
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serotonin / pharmacology*
  • Synapses / drug effects
  • Synapses / physiology


  • 3' Untranslated Regions
  • CCAAT-Enhancer-Binding Proteins
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Serotonin
  • Luciferases