title: Splicing factor transformer-2β (Tra2β) regulates the expression of regulator of G protein signaling 4 (RGS4) gene and is induced by morphine.
abstract: Regulator of G protein signaling 4 (RGS4) is a critical modulator of G protein-coupled receptor (GPCR)-mediated signaling and plays important roles in many neural process and diseases. Particularly, drug-induced alteration in RGS4 protein levels is associated with acute and chronic effects of drugs of abuse. However, the precise mechanism underlying the regulation of RGS4 expression is largely unknown. Here, we demonstrated that the expression of RGS4 gene was subject to regulation by alternative splicing of the exon 6. Transformer-2β (Tra2β), an important splicing factor, bound to RGS4 mRNA and increased the relative level of RGS4-1 mRNA isoform by enhancing the inclusion of exon 6. Meanwhile, Tra2β increased the expression of full-length RGS4 protein. In rat brain, Tra2β was co-localized with RGS4 in multiple opioid action-related brain regions. In addition, the acute and chronic morphine treatment induced alteration in the expression level of Tra2β in rat locus coerulus (LC) in parallel to that of RGS4 proteins. It suggests that induction of this splicing factor may contribute to the change of RGS4 level elicited by morphine. Taken together, the results provide the evidence demonstrating the function of Tra2β as a new mediator in opioid-induced signaling pathway via regulating RGS4 expression.
authors: State Key Laboratory of Medical Neurobiology and Department of Neurobiology,School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, China.
authors: Shu-Jing
authors: SJ
authors: Li
authors: Ya
authors: Y
authors: Li
authors: Shi-chao
authors: SC
authors: Cui
authors: Yao
authors: Y
authors: Qi
authors: Jing-Jing
authors: JJ
authors: Zhao
authors: Xiao-Yan
authors: XY
authors: Liu
authors: Ping
authors: P
authors: Xu
authors: Xian-Hua
authors: XH
authors: Chen
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001931:Brain Mapping; D005091:Exons; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D020710:RGS Proteins / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068103:Serine-Arginine Splicing Factors; D015398:Signal Transduction
chemical_list: D009419:Nerve Tissue Proteins; D020710:RGS Proteins; D016601:RNA-Binding Proteins; C490770:Tra2b protein, rat; D049452:Green Fluorescent Proteins; D000068103:Serine-Arginine Splicing Factors; C098799:RGS4 protein; D009020:Morphine
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