RNA editing and alternative splicing of human serotonin 2C receptor in schizophrenia.
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.
Dracheva
Stella
S
Department of Psychiatry, Mount Sinai School of Medicine and Bronx Veterans Affairs Medical Center, New York 10468, USA.
Elhakem
Sharif L
SL
Marcus
Sue M
SM
Siever
Larry J
LJ
McGurk
Susan R
SR
Haroutunian
Vahram
V
D000241:Adenosine / Q000235:genetics; D000368:Aged; D017398:Alternative Splicing; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007288:Inosine / Q000235:genetics; D008297:Male; D017397:Prefrontal Cortex / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017393:RNA Editing; D012333:RNA, Messenger / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism
D020033:Protein Isoforms; D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C; D007288:Inosine; D000241:Adenosine