Novel function of neuron-restrictive silencer factor (NRSF) for posttranscriptional regulation.
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).
Kim
Chun Sung
CS
Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA. cskim2@chosun.ac.kr
Hwang
Cheol Kyu
CK
Song
Kyu Young
KY
Choi
Hack Sun
HS
Kim
Do Kyung
DK
Law
Ping-Yee
PY
Wei
Li-Na
LN
Loh
Horace H
HH
D000818:Animals; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008024:Ligands; D010766:Phosphorylation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017450:Receptors, Opioid, mu / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D000099229:RE1-Silencing Transcription Factor
D008024:Ligands; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D012097:Repressor Proteins; D000099229:RE1-Silencing Transcription Factor