A rapid new assay to detect RNA editing reveals antipsychotic-induced changes in serotonin-2C transcripts.
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.
Sodhi
Monsheel S K
MS
Department of Psychiatry and Pharmacology, Vanderbilt University, 8148 Medical Research Building III, 465 21st Avenue South, Nashville, TN 37212, USA. monsheel. sodhi@vanderbilt.edu
Airey
David C
DC
Lambert
Warren
W
Burnet
Philip W J
PW
Harrison
Paul J
PJ
Sanders-Bush
Elaine
E
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001483:Base Sequence; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D016000:Cluster Analysis; D017931:DNA Primers; D008297:Male; D017393:RNA Editing; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects* / Q000378:metabolism
D014150:Antipsychotic Agents; D017931:DNA Primers; D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C