Morphine drives internal ribosome entry site-mediated hnRNP K translation in neurons through opioid receptor-dependent signaling

Pin Tse Lee, Po Kuan Chao, Li Chin Ou, Jian Ying Chuang, Yen Chang Lin, Shu Chun Chen, Hsiao Fu Chang, Ping Yee Law, Horace H. Loh, Yu Sheng Chao, Tsung Ping Su, Shiu Hwa Yeh

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 languageEnglish
Pages (from-to)13012-13025
Number of pages14
JournalNucleic Acids Research
Volume42
Issue number21
DOIs
Publication statusPublished - Dec 1 2014

Fingerprint

Heterogeneous-Nuclear Ribonucleoprotein K
Opioid Receptors
Morphine
Neurons
mu Opioid Receptor
Internal Ribosome Entry Sites
HEK293 Cells
5' Untranslated Regions
Genetic Promoter Regions
Knockout Mice
Membrane Potentials
Analgesia
Small Interfering RNA
Analgesics
Spinal Cord
Proteins
Down-Regulation
Central Nervous System

ASJC Scopus subject areas

  • Genetics

Cite this

Morphine drives internal ribosome entry site-mediated hnRNP K translation in neurons through opioid receptor-dependent signaling. / Lee, Pin Tse; Chao, Po Kuan; Ou, Li Chin; Chuang, Jian Ying; Lin, Yen Chang; Chen, Shu Chun; Chang, Hsiao Fu; Law, Ping Yee; Loh, Horace H.; Chao, Yu Sheng; Su, Tsung Ping; Yeh, Shiu Hwa.

In: Nucleic Acids Research, Vol. 42, No. 21, 01.12.2014, p. 13012-13025.

Research output: Contribution to journalArticle

Lee, PT, Chao, PK, Ou, LC, Chuang, JY, Lin, YC, Chen, SC, Chang, HF, Law, PY, Loh, HH, Chao, YS, Su, TP & Yeh, SH 2014, 'Morphine drives internal ribosome entry site-mediated hnRNP K translation in neurons through opioid receptor-dependent signaling', Nucleic Acids Research, vol. 42, no. 21, pp. 13012-13025. https://doi.org/10.1093/nar/gku1016
Lee, Pin Tse ; Chao, Po Kuan ; Ou, Li Chin ; Chuang, Jian Ying ; Lin, Yen Chang ; Chen, Shu Chun ; Chang, Hsiao Fu ; Law, Ping Yee ; Loh, Horace H. ; Chao, Yu Sheng ; Su, Tsung Ping ; Yeh, Shiu Hwa. / Morphine drives internal ribosome entry site-mediated hnRNP K translation in neurons through opioid receptor-dependent signaling. In: Nucleic Acids Research. 2014 ; Vol. 42, No. 21. pp. 13012-13025.
@article{667e881d31d94851940b37b3c50ff294,
title = "Morphine drives internal ribosome entry site-mediated hnRNP K translation in neurons through opioid receptor-dependent signaling",
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.",
author = "Lee, {Pin Tse} and Chao, {Po Kuan} and Ou, {Li Chin} and Chuang, {Jian Ying} and Lin, {Yen Chang} and Chen, {Shu Chun} and Chang, {Hsiao Fu} and Law, {Ping Yee} and Loh, {Horace H.} and Chao, {Yu Sheng} and Su, {Tsung Ping} and Yeh, {Shiu Hwa}",
year = "2014",
month = "12",
day = "1",
doi = "10.1093/nar/gku1016",
language = "English",
volume = "42",
pages = "13012--13025",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "21",

}

TY - JOUR

T1 - Morphine drives internal ribosome entry site-mediated hnRNP K translation in neurons through opioid receptor-dependent signaling

AU - Lee, Pin Tse

AU - Chao, Po Kuan

AU - Ou, Li Chin

AU - Chuang, Jian Ying

AU - Lin, Yen Chang

AU - Chen, Shu Chun

AU - Chang, Hsiao Fu

AU - Law, Ping Yee

AU - Loh, Horace H.

AU - Chao, Yu Sheng

AU - Su, Tsung Ping

AU - Yeh, Shiu Hwa

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84945236727&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84945236727&partnerID=8YFLogxK

U2 - 10.1093/nar/gku1016

DO - 10.1093/nar/gku1016

M3 - Article

C2 - 25361975

AN - SCOPUS:84945236727

VL - 42

SP - 13012

EP - 13025

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 21

ER -