Regulation of serotonin-2C receptor G-protein coupling by RNA editing
Regulation of serotonin-2C receptor G-protein coupling by RNA editing
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DOI：
10.1038/387303a0
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发表时间：
1997-05-15
期刊：
影响因子：
64.8
通讯作者：
Emeson, RB
中科院分区：
文献类型：
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作者：
Burns, CM;Chu, H;Emeson, RB
神经递质5-羟色胺（5-羟色胺，5-HT）通过与几种受体亚型结合而引起广泛的生理效应。5-HT2受体家族属于一个由7个跨膜g蛋白偶联受体组成的大群体，包括3种受体亚型（5-HT2A、5-HT2B和5-HT2C），它们与磷脂酶C相连，促进膜磷脂的水解，并随后增加细胞内磷酸肌醇和二酰基甘油的水平(1)。本研究表明，编码5-羟色胺受体2C亚型（5-HT2CR）的转录本经历RNA编辑事件，其中基因组编码的腺苷残基通过双链RNA腺苷脱氨酶(s)的作用转化为肌苷。从解剖脑区分离的互补DNA序列分析表明，由11种不同RNA种编码的7种主要5-HT2C受体亚型具有组织特异性表达。J-HT2CR信使rna的编辑改变了预测的受体细胞内第二环的氨基酸编码电位，并可能导致受体与其G蛋白之间相互作用的功效降低10-15倍。这些观察结果表明，RNA编辑是调节血清素能信号转导的新机制，并表明这种转录后修饰可能对调节由g蛋白偶联受体超家族其他成员介导的不同细胞功能至关重要。
The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) elicits a wide array of physiological effects by binding to several receptor subtypes. The 5-HT2 family of receptors belongs to a large group of seven-transmembrane-spanning G-protein-coupled receptors and includes three receptor subtypes (5-HT2A, 5-HT2B and 5-HT2C) which are linked to phospholipase C, promoting the hydrolysis of membrane phospholipids and a subsequent increase in the intracellular levels of inositol phosphates and diacylglycerol(1). Here we show that transcripts encoding the 2C subtype of serotonin receptor (5-HT2CR) undergo RNA editing events in which genomically encoded adenosine residues are converted to inosines by the action of double-stranded RNA adenosine deaminase(s). Sequence analysis of complementary DNA isolates from dissected brain regions have indicated the tissue-specific expression of seven major 5-HT2C receptor isoforms encoded by eleven distinct RNA species. Editing of J-HT2CR messenger RNAs alters the amino-acid coding potential of the predicted second intracellular loop of the receptor and can lead to a 10-15-fold reduction in the efficacy of the interaction between receptors and their G proteins. These observations indicate that RNA editing is a new mechanism for regulating serotonergic signal transduction and suggest that this post-transcriptional modification may be critical for modulating the different cellular functions that are mediated by other members of the G-protein-coupled receptor superfamily.