Differential A-to-I RNA editing of the serotonin-2C receptor G-protein-coupled, HTR2C, in porcine brain tissues

• A-to-I HTR2C transcript editing is conserved between pig and human.
• A differential HTR2C transcript editing is observed in pig brain.
• An age-related increase in A-to-I editing of HTR2C mRNA was found.
• HTR2C mRNA is exclusively expressed in pig brain.
• The HTR2C gene was mapped to pig chromosome X.

The HTR2C gene encodes the 5-Hydroxytryptamine (serotonin) receptor 2C, G-protein-coupled protein which functions as a serotonin receptor. The HTR2C mRNA is subject to A-to-I RNA editing mediated by adenosine deaminases acting on RNA 1 and 2 (ADAR1 and ADAR2). In the current study we examined the molecular characteristics of the porcine HTR2C gene and determined the mRNA editing of the HTR2C transcript in different tissues. The A-to-I RNA editing of HTR2C was shown to be conserved in the porcine homologue with five nucleotides edited in exon 5. A differential editing was demonstrated with a high editing frequency in the frontal cortex, parietal cortex, occipital cortex, hypothalamus, brain stem and spinal cord and significantly lower in the cerebellum. No editing was seen in the liver and kidney. The porcine HTR2C gene was found to be exclusively expressed in brain tissues. The HTR2C gene was mapped to pig chromosome X. The methylation status of the HTR2C gene was examined in brain and liver by bisulfate sequencing and a high degree of methylation was found in the two tissues, at 89 and 72%, respectively. Our data describe differences in RNA editing in various regions of the porcine brain. The differences might reflect functional differences. Similarities between pigs and humans in differential RNA editing support the use of the pig as a model organism for the study of neurological diseases.