PMID- 20874756 OWN - NLM STAT- MEDLINE DCOM- 20101129 LR - 20131121 IS - 1471-4159 (Electronic) IS - 0022-3042 (Linking) VI - 115 IP - 5 DP - 2010 Dec TI - Involvement of the 3'-untranslated region of the brain-derived neurotrophic factor gene in activity-dependent mRNA stabilization. PG - 1222-33 LID - 10.1111/j.1471-4159.2010.07016.x [doi] AB - Although gene transcription is controlled by neuronal activity, little is known about post-transcriptional regulation in neurons. Using cultured neurons, we found that the half-life of immediate-early gene transcripts is prolonged or shortened by membrane depolarization. Focusing on the activity-dependent stabilization of brain-derived neurotrophic factor (BDNF) mRNA, we constructed a series of plasmids, in which the short 3'-untranslated region (3'-UTR) of the BDNF gene was fused to the firefly luciferase gene, and found that the 3'-UTR prevented destabilization of luciferase mRNA through Ca(2+) signals evoked via depolarization. No such prevention was observed with the simian virus 40 late poly(A) site. The pre-mRNA covering the entire short 3'-UTR, where multiple poly(A) sites including novel ones are located, was stabilized. Deletion analyses of 3'-UTR revealed a core region (about 130 bases long) and a complementary region to be responsible for the prevention, well consistent with the formation of an extended stem-loop RNA structure and the production of poly(A) mRNAs. Thus, the mRNA stability is activity-dependently controlled in neurons and distinct regions of the 3'-UTR of BDNF mRNA are involved in stabilizing mRNA in response to Ca(2+) signals, suggesting a primary role of the RNA secondary structure affecting the availability of poly(A) sites in activity-dependent mRNA stabilization. CI - (c) 2010 The Authors. Journal of Neurochemistry (c) 2010 International Society for Neurochemistry. FAU - Fukuchi, Mamoru AU - Fukuchi M AD - Department of Biological Chemistry, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan. FAU - Tsuda, Masaaki AU - Tsuda M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101026 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (3' Untranslated Regions) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Calcium Channel Blockers) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (Protein Synthesis Inhibitors) RN - 0 (RNA Precursors) RN - 0 (RNA, Messenger) RN - 0 (brain-derived growth factor) RN - 1CC1JFE158 (Dactinomycin) RN - 76326-31-3 (2-amino-5-phosphopentanoic acid) RN - CZ5312222S (Nicardipine) RN - HG18B9YRS7 (Valine) SB - IM MH - 3' Untranslated Regions/*physiology MH - Animals MH - Brain-Derived Neurotrophic Factor/*genetics/metabolism MH - Calcium Channel Blockers/pharmacology MH - Calcium Signaling/drug effects/genetics MH - Cells, Cultured MH - Cerebral Cortex/cytology MH - Dactinomycin/pharmacology MH - Embryo, Mammalian MH - Excitatory Amino Acid Antagonists/pharmacology MH - Gene Expression Regulation/*genetics MH - Genes, Immediate-Early/physiology MH - Neurons MH - Nicardipine/pharmacology MH - Protein Synthesis Inhibitors/pharmacology MH - RNA Precursors/genetics/metabolism MH - RNA, Messenger/*metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Transfection/methods MH - Valine/analogs & derivatives/pharmacology EDAT- 2010/09/30 06:00 MHDA- 2010/12/14 06:00 CRDT- 2010/09/30 06:00 PHST- 2010/09/30 06:00 [entrez] PHST- 2010/09/30 06:00 [pubmed] PHST- 2010/12/14 06:00 [medline] AID - 10.1111/j.1471-4159.2010.07016.x [doi] PST - ppublish SO - J Neurochem. 2010 Dec;115(5):1222-33. doi: 10.1111/j.1471-4159.2010.07016.x. Epub 2010 Oct 26.