Abstract
Heterogeneous nuclear ribonucleoprotein K (hnRNP K) binds to the promoter region of mu-opioid receptor (MOR) to regulate its transcriptional activity. How hnRNP K contributes to the analgesic effects of morphine, however, is largely unknown. We provide evidence that morphine increases hnRNP K protein expression via MOR activation in rat primary cortical neurons and HEK-293 cells expressing MORs, without increasing mRNA levels. Using the bicistronic reporter assay, we examined whether morphine-mediated accumulation of hnRNP K resulted from translational control. We identified potential internal ribosome entry site elements located in the 5′ untranslated regions of hnRNP K transcripts that were regulated by morphine. This finding suggests that internal translation contributes to the morphine-induced accumulation of hnRNP K protein in regions of the central nervous system correlated with nociceptive and antinociceptive modulatory systems in mice. Finally, we found that down-regulation of hnRNP K mediated by siRNA attenuated morphine-induced hyperpolarization of membrane potential in AtT20 cells. Silencing hnRNP K expression in the spinal cord increased nociceptive sensitivity in wild-type mice, but not in MOR-knockout mice. Thus, our findings identify the role of translational control of hnRNP K in morphine-induced analgesia through activation of MOR.
Original language | English (US) |
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Pages (from-to) | 13012-13025 |
Number of pages | 14 |
Journal | Nucleic acids research |
Volume | 42 |
Issue number | 21 |
DOIs | |
State | Published - Dec 1 2014 |
Bibliographical note
Funding Information:Intramural Research Program of National Health Research Institutes, Taiwan, Republic of China; and Ministry of Science and Technology, Taiwan, Republic of China [NSC 101–2325-B-400–005, NSC 102–2325-B-400– 005, NSC 103–2325-B-400–018, NSC 101–2311-B-400– 005-MY3 and NSC 101–2320-B-034–001]. Funding for open access charge: Ministry of Science and Technology, Taiwan, Republic of China [NSC 103–2325-B-400–018]. Conflict of interest statement. None declared.
Publisher Copyright:
© 2014 The Author(s).