PMID- 18657578 OWN - NLM STAT- MEDLINE DCOM- 20081113 LR - 20161126 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1783 IP - 10 DP - 2008 Oct TI - Novel function of neuron-restrictive silencer factor (NRSF) for posttranscriptional regulation. PG - 1835-46 LID - 10.1016/j.bbamcr.2008.06.019 [doi] AB - The neuron-restrictive silencer factor (NRSF) functions as a transcriptional repressor of neuronal genes in nonneuronal cells. However, it is expressed in certain mature neurons in adults, suggesting that it might have complex and novel roles depending on its cellular and physiological context. Overexpression of NRSF led to both increased opioid ligand-binding activity of the endogenous MOR and MOR-GFP fusion protein expression. In RNA immunoprecipitation and gel-shift assays, NRSF specifically interacted with the NRSE sequence of MOR mRNA. When MOR and NRSF genes were coexpressed, the specific ligand-binding activity of MOR was increased in neuroblastoma NMB cells, but decreased in PC12 cells result from its localization. Indeed, after overexpressing NRSF in NMB cells, the target RNA moved to the translationally active polysomal fraction. Overexpression of NRSF also led to enhanced phosphorylation of eIF4G. In contrast, knockdown of NRSF by siRNA transfection significantly decreased eIF4G phosphorylation. These findings indicate that NRSF may deliver the target MOR transcripts to the polyribosomal complex and activate eIF4G phosphorylation, resulting in translational activation. We report here a novel function of NRSF that enhance the translation of the mu opioid receptor (MOR) gene through its RNA binding sequence, the neuron-restrictive silencer element (NRSE). FAU - Kim, Chun Sung AU - Kim CS AD - Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA. cskim2@chosun.ac.kr FAU - Hwang, Cheol Kyu AU - Hwang CK FAU - Song, Kyu Young AU - Song KY FAU - Choi, Hack Sun AU - Choi HS FAU - Kim, Do Kyung AU - Kim DK FAU - Law, Ping-Yee AU - Law PY FAU - Wei, Li-Na AU - Wei LN FAU - Loh, Horace H AU - Loh HH LA - eng GR - DA000564/DA/NIDA NIH HHS/United States GR - DA001583/DA/NIDA NIH HHS/United States GR - DA011190/DA/NIDA NIH HHS/United States GR - DA011806/DA/NIDA NIH HHS/United States GR - DA013926/DA/NIDA NIH HHS/United States GR - K05-DA070554/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20080708 PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (Ligands) RN - 0 (RE1-silencing transcription factor) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Opioid, mu) RN - 0 (Repressor Proteins) SB - IM MH - Animals MH - Cell Line, Tumor MH - Cytoplasm/metabolism MH - Gene Expression Regulation/*genetics MH - Genes, Reporter/genetics MH - Humans MH - Ligands MH - Phosphorylation MH - Protein Biosynthesis MH - RNA, Messenger/genetics MH - Rats MH - Receptors, Opioid, mu/metabolism MH - Repressor Proteins/genetics/*metabolism EDAT- 2008/07/29 09:00 MHDA- 2008/11/14 09:00 CRDT- 2008/07/29 09:00 PHST- 2008/01/04 00:00 [received] PHST- 2008/06/19 00:00 [revised] PHST- 2008/06/20 00:00 [accepted] PHST- 2008/07/29 09:00 [pubmed] PHST- 2008/11/14 09:00 [medline] PHST- 2008/07/29 09:00 [entrez] AID - S0167-4889(08)00243-7 [pii] AID - 10.1016/j.bbamcr.2008.06.019 [doi] PST - ppublish SO - Biochim Biophys Acta. 2008 Oct;1783(10):1835-46. doi: 10.1016/j.bbamcr.2008.06.019. Epub 2008 Jul 8.