Post-transcriptional regulation of mu-opioid receptor: role of the RNA-binding proteins heterogeneous nuclear ribonucleoprotein H1 and F

Cell Mol Life Sci. 2012 Feb;69(4):599-610. doi: 10.1007/s00018-011-0761-z. Epub 2011 Jul 8.


Classical opioids have been historically used for the treatment of pain and are among the most widely used drugs for both acute severe pain and long-term pain. Morphine and endogenous mu-opioid peptides exert their pharmacological actions mainly through the mu-opioid receptor (MOR). However, the expression of opioid receptor (OR) proteins is controlled by extensive transcriptional and post-transcriptional processing. Previously, the 5'-untranslated region (UTR) of the mouse MOR was found to be important for post-transcriptional regulation of the MOR gene in neuronal cells. To identify proteins binding to the 5'-UTR as potential regulators of the mouse MOR gene, affinity column chromatography using 5'-UTR-specific RNA oligonucleotides was performed using neuroblastoma NS20Y cells. Chromatography was followed by two-dimensional gel electrophoresis and MALDI-TOF mass spectrometry. We identified two heterogeneous ribonucleoproteins (hnRNPs) that bound to RNA sequences of interest: hnRNP H1 and hnRNP F. Binding of these proteins to the RNA region was M4-region sequence-specific as confirmed by Western-blot analysis and RNA supershift assay. Furthermore, a cotransfection study showed that the presence of hnRNP H1 and F resulted in repressed expression of the mouse MOR. Our data suggest that hnRNP H1 and F can function as repressors of MOR translation dependent on the M4 (-75 to -71 bp upstream of ATG) sequences. We demonstrate for the first time a role of hnRNPs as post-transcriptional repressors in MOR gene regulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Animals
  • Base Sequence
  • Cell Line
  • Chromatography, Affinity
  • Electrophoresis, Gel, Two-Dimensional
  • Gene Expression Regulation
  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H / metabolism
  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H / physiology*
  • Mice
  • Molecular Sequence Data
  • Oligonucleotides / chemistry
  • Oligonucleotides / metabolism
  • RNA Processing, Post-Transcriptional
  • Receptors, Opioid, mu / genetics
  • Receptors, Opioid, mu / metabolism*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • 5' Untranslated Regions
  • Heterogeneous-Nuclear Ribonucleoprotein Group F-H
  • Oligonucleotides
  • Receptors, Opioid, mu