RNA editing and alternative splicing of human serotonin 2C receptor in schizophrenia
RNA editing and alternative splicing of human serotonin 2C receptor in schizophrenia
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DOI：
10.1046/j.1471-4159.2003.02115.x
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发表时间：
2003-12-01
影响因子：
4.7
通讯作者：
Haroutunian, V
中科院分区：
文献类型：
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作者：
Dracheva, S;Elhakem, SL;Haroutunian, V
大脑中5-羟色胺2C受体（5-HT2CR）的异质性主要来自两个不同的来源：(i) 5-HT2CR mRNA在五个位置经历腺苷-肌苷编辑事件，导致氨基酸取代，产生具有不同药理特性的受体变体；（ii） 5-HT2CR mRNA被选择性剪接，导致截断的mRNA异构体（5-HT2CR-tr）编码无功能的5-羟色胺受体。我们分析了老年精神分裂症患者前额叶皮层中5-HT2CR mRNA的编辑效率以及全长和截断的5-HT2CR mRNA剪接异构体的表达（ns = 15）。未发现显著差异，表明在接受抗精神病药物治疗的患者中，与精神分裂症相关的5-HT(2C)Rs的编辑或选择性剪接没有改变。5-HT2CR和5-HT2CR-tr mRNA变异的定量显示，5-HT2CR-tr的表达与全长亚型的50%相似。
Serotonin 2C receptor (5-HT2CR) heterogeneity in the brain occurs mostly from two different sources: (i) 5-HT2CR mRNA undergoes adenosine-to-inosine editing events at five positions, which leads to amino acid substitutions that produce receptor variants with different pharmacological properties; (ii) 5-HT2CR mRNA is alternatively spliced, resulting in a truncated mRNA isoform (5-HT2CR-tr) which encodes a non-functional serotonin receptor. 5-HT2CR mRNA editing efficiencies and the expression of the full-length and the truncated 5-HT2CR mRNA splice isoforms were analyzed in the prefrontal cortex of elderly subjects with schizophrenia vs. matched controls (ns = 15). No significant differences were found, indicating that there are no alterations in editing or alternative splicing of 5-HT(2C)Rs that are associated with schizophrenia in persons treated with antipsychotic medications. Quantitation of 5-HT2CR and 5-HT2CR-tr mRNA variants revealed that the expression of 5-HT2CR-tr was similar to 50% of that observed for the full-length isoform.