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Phosphorylation of Yin Yang 1 mediates fentanyl‐induced decrease in miR‐190 expression
Author(s) -
Zheng Hui,
Chu Ji,
Zeng Yan,
Loh Horace H,
Law PingYee
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.855.11
Subject(s) - phosphorylation , agonist , fentanyl , chemistry , microrna , mapk/erk pathway , transcription factor , microbiology and biotechnology , signal transduction , yy1 , downregulation and upregulation , promoter , gene expression , receptor , biology , pharmacology , gene , biochemistry
G protein‐coupled receptor exhibits agonist‐selective signaling. μ‐opioid receptor agonists (morphine and fentanyl) utilize G protein‐ and β‐arrestin‐dependent pathways respectively in ERK activation, which leads to the differential regulation of microRNAs. microRNA microarray has identified miR‐190 as one microRNA under agonist‐selective regulation. Fentanyl, but not morphine, decreases hippocampal miR‐190 level in a concentration‐ and time‐dependent manner. Fentanyl suppresses miR‐190 expression by decreasing the transcription of miR‐190's host gene, talin2 . Fentanyl‐mediated regulation of the Talin2 promoter activity is located at the − 208~− 200 region on the promoter. Mutating this region attenuated fentanyl‐induced decrease in Talin2 promoter activity. The − 208~− 200 region contains a binding site for Yin Yang 1 (YY1). YY1 overexpression increased, while YY1 downregulation decreased, the transcription of talin2. Fentanyl‐induced ERK phosphorylation led to YY1 phosphorylation, which decreased YY1's ability to stimulate talin2 transcription or to increase miR‐190 expression, by impairing its association with the − 208~− 200 region as demonstrated with the EMSA and ChIP assays. This study, therefore, delineates the signaling pathway in which fentanyl (but not morphine) regulates miR‐190 expression. (This research is supported in parts by a NIDA grant DA007339).