Novel function of neuron-restrictive silencer factor (NRSF) for posttranscriptional regulation

Chun Sung Kim, Cheol Kyu Hwang, Kyu Young Song, Hack Sun Choi, Do Kyung Kim, Ping Yee Law, Li Na Wei, Horace H. Loh

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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).

Original languageEnglish (US)
Pages (from-to)1835-1846
Number of pages12
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1783
Issue number10
DOIs
StatePublished - Oct 2008

Bibliographical note

Funding Information:
We would like to thank David J. Anderson for the mouse monoclonal NRSF antibody, Avtar Roopra for the MYC-tagged NRSF expression plasmids. This work was supported by National Institutes of Health Research Grants DA000564, DA001583, DA011806, K05-DA070554, DA011190, DA013926, and by the A&F Stark Fund of the Minnesota Medical Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Keywords

  • Mu opioid receptor
  • NRSE
  • NRSF
  • Translational regulation
  • eIF4G

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