Editing

The 5-HT2C receptor pre-messenger ribonucleic acid (pre-mRNA) undergoes both editing and alternative pre-mRNA splicing. Both events occur in the cell nucleous and are summarized below. RNA editing is the chemical modification of RNA bases. Common editing events include 2'-O-methylation, the addition of a methyl group on the ribose; conversion of cytidine to uridine; and conversion from adenine to inosine. The modification of the bases is catalyzed by deaminating enzymes that hydrolyze specific amino groups of the bases. The cytidine-to-uridine editing is catalyzed by cytidine deaminase, and the ade-nine-to-inosine editing is catalyzed by adenosine deaminase acting on RNAs (ADARs) (reviewed in Jepson and Reenan 2008 and Mehler and Mattick 2007). Editing of RNA has multiple effects on the resulting RNAs. It can lead to alteration of coding capacity, altered microRNA (miRNA) or small inhibitory RNA (siRNA) target populations, heterochromatin formation, nuclear sequestration, cytoplasmic sequestration, inhibition of miRNA and siRNA processing, and altered alternative splicing patterns (Nishikura 2006). The 5-HT2C receptor pre-mRNA undergoes adenine-to-inosine editing on at least five editing sites. The combination of these sites could generate 32 isoforms theoretically, but not all the predicted mRNA forms have been identified (reviewed in Werry et al. 2008). As the translational machinery interprets an inosine as a guanosine the adenine-to-guanine editing changes the protein sequence that is encoded by the edited pre-mRNA. Due to the degeneracy of the genetic code, some of the edited mRNAs encode the same protein, which reduced the number to proteins generated by editing to 24.

Department of Molecular and Cellular Biochemistry, University of Kentucky, College of Medicine, B283 Biomedical Biological Sciences Research Building, 741 South Limestone, Lexington, KY 40536-0509, USA e-mail: [email protected]

G. Di Giovanni et al. (eds.), 5-HT2C Receptors in the Pathophysiology of CNS Disease, 413 The Receptors 22, DOI 10.1007/978-1-60761-941-3_21, © Springer Science+Business Media, LLC 2011

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