A rapid new assay to detect RNA editing reveals antipsychotic-induced changes in serotonin-2C transcripts.

Journal article

We report the development of a new assay as an alternative to direct DNA sequencing to measure RNA-edited variation in tissue. The new assay has been validated and is accurate, cheaper, more rapid, and less labor-intensive than DNA sequencing. We also outline the statistical modeling required for analyses of the hierarchical, clustered RNA-editing data generated in these studies. Using the new technique, we analyzed the effects of long-term antipsychotic medication on serotonin-2C receptor (5-HT2CR) RNA editing in rat brain. Our hypothesis that a drug with high affinity for 5-HT2CR, such as clozapine, would alter its RNA-editing profile was not confirmed. Whereas haloperidol, a typical antipsychotic drug that is primarily a dopamine receptor antagonist, reduced 5-HT2C VNV isoform frequency and the level of RNA editing at the D site, risperidone and not the prototype atypical antipsychotic drug clozapine increased the frequency of 5-HT2C VNV and D-site editing. Our data emphasize that caution is required in the interpretation of RNA-editing data in studies of psychiatric disorders, because these studies usually include subjects who received long-term exposure to medication. This newly established method will facilitate high-throughput investigations of RNA editing in disease pathology and in the pharmacological activity of drugs.

Authors: Sodhi, MS; Airey, D; Lambert, W; Burnet, P; Harrison, P

• Publication status: Published
• Journal: Molecular pharmacology
• Volume: 68
• Issue: 3
• Pages: 711-719
• Publication date: 2005-09-01
• DOI: 10.1124/mol.105.014134
• EISSN: 1521-0111
• ISSN: 0026-895X
• Language: English
• Keywords: RNA, Messenger; Rats; RNA Editing; Animals; Base Sequence; DNA Primers; Rats, Sprague-Dawley; Male; Brain; Antipsychotic Agents; Receptor, Serotonin, 5-HT2C; Cluster Analysis