RNA editing and alternative splicing of human serotonin 2C receptor in schizophrenia |
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Authors: | Dracheva Stella Elhakem Sharif L Marcus Sue M Siever Larry J McGurk Susan R Haroutunian Vahram |
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Affiliation: | Department of Psychiatry, Mount Sinai School of Medicine and Bronx Veterans Affairs Medical Center, New York 10468, USA. |
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Abstract: | 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-HT2CRs 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 approximately 50% of that observed for the full-length isoform. |
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Keywords: | alternative splicing dorsolateral prefrontal cortex real-time PCR RNA editing schizophrenia serotonin 2C receptor |
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