title: AU-rich element-binding protein negatively regulates CCAAT enhancer-binding protein mRNA stability during long-term synaptic plasticity in Aplysia.
abstract: The consolidation of long-term memory for sensitization and synaptic facilitation in Aplysia requires synthesis of new mRNA including the immediate early gene Aplysia CCAAT enhancer-binding protein (ApC/EBP). After the rapid induction of ApC/EBP expression in response to repeated treatments of 5-hydroxytryptamine (5-HT), ApC/EBP mRNA is temporarily expressed in sensory neurons of sensory-to-motor synapses. However, the molecular mechanism underlying the rapid degradation of ApC/EBP transcript is not known. Here, we cloned an AU-rich element (ARE)-binding protein, ApAUF1, which functions as a destabilizing factor for ApC/EBP mRNA. ApAUF1 was found to bind to the 3' UTR of ApC/EBP mRNA that contains AREs and subsequently reduces the expression of ApC/EBP 3' UTR-containing reporter genes. Moreover, overexpression of ApAUF1 inhibited the induction of ApC/EBP mRNA in sensory neurons and also impaired long-term facilitation of sensory-to-motor synapses by repetitive 5-HT treatments. These results provide evidence for a critical role of the posttranscriptional modification of ApC/EBP mRNA during the consolidation of synaptic plasticity.
authors.affiliation: National Creative Research Initiative Center for Memory, Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, Korea.
authors.forename: Yong-Seok
authors.initials: YS
authors.lastname: Lee
authors.forename: Sun-Lim
authors.initials: SL
authors.lastname: Choi
authors.forename: Heejung
authors.initials: H
authors.lastname: Jun
authors.forename: Se-Jeong
authors.initials: SJ
authors.lastname: Yim
authors.forename: Jin-A
authors.initials: JA
authors.lastname: Lee
authors.forename: Hyoung F
authors.initials: HF
authors.lastname: Kim
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Shim
authors.forename: Kyungmin
authors.initials: K
authors.lastname: Lee
authors.forename: Deok-Jin
authors.initials: DJ
authors.lastname: Jang
authors.forename: Bong-Kiun
authors.initials: BK
authors.lastname: Kaang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001048:Aplysia; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D008954:Models, Biological; D008957:Models, Genetic; D009473:Neuronal Plasticity; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D020413:3' Untranslated Regions; D022762:CCAAT-Enhancer-Binding Proteins; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D012333:RNA, Messenger