Schmauss Claudia
Department of Psychiatry and Neuroscience, Columbia University College of Physicians & Surgeons, New York State Psychiatric Institute, USA.
Neuroscientist. 2003 Aug;9(4):237-42. doi: 10.1177/1073858403253669.
Transcripts of the gene encoding the serotonin 2C receptor are modified by RNA editing, a posttranscriptional process that converts adenosines to inosines. This editing changes up to three genomically encoded amino acids located in the second intracellular loop of the G-protein-coupled receptor. Compared with nonedited receptors, extensively edited receptor isoforms activate G protein less efficiently. Studies on mice revealed that 5-HT2C pre-mRNA editing is regulated in a serotonin-dependent manner, and postmortem studies on brain tissues of patients with schizophrenia and major depression found distinct site-specific alterations of this editing in the prefrontal cortex, a brain region expressing a large number of differently edited 5-HT2C mRNA isoforms. At present, the most complex alterations in 5-HT2C pre-mRNA editing were found in brains of depressed suicide victims. In these brains, 5-HT2C receptor isoforms with reduced function are expressed at significantly increased levels, suggesting that the regulation of editing by synaptic serotonin is defective.
血清素2C受体编码基因的转录本通过RNA编辑进行修饰，这是一种将腺苷转化为肌苷的转录后过程。这种编辑可改变位于G蛋白偶联受体第二个细胞内环中的多达三个基因组编码氨基酸。与未编辑的受体相比，广泛编辑的受体异构体激活G蛋白的效率较低。对小鼠的研究表明，5-HT2C前体mRNA编辑以血清素依赖的方式受到调节，对精神分裂症和重度抑郁症患者脑组织的死后研究发现，前额叶皮质（一个表达大量不同编辑的5-HT2C mRNA异构体的脑区）中这种编辑存在明显的位点特异性改变。目前，在抑郁自杀受害者的大脑中发现了5-HT2C前体mRNA编辑中最复杂的改变。在这些大脑中，功能降低的5-HT2C受体异构体表达水平显著增加，这表明突触血清素对编辑的调节存在缺陷。
