Serotonin 2C receptors: suicide, serotonin, and runaway RNA editing.
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.
Schmauss
Claudia
C
Department of Psychiatry and Neuroscience, Columbia University College of Physicians & Surgeons, New York State Psychiatric Institute, USA. schmauss@neuron.cpmc.columbia.edu
D000818:Animals; D001921:Brain / Q000502:physiology; D003863:Depression / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D020033:Protein Isoforms / Q000235:genetics* / Q000378:metabolism; D017393:RNA Editing / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics*; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000235:genetics* / Q000378:metabolism; D012559:Schizophrenia / Q000235:genetics; D012701:Serotonin / Q000378:metabolism*; D013405:Suicide
D020033:Protein Isoforms; D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012701:Serotonin