Messenger RNA Editing of the Human Serotonin 5-HT2C Receptor

Enhancement of alcohol drinking in mice depends on alterations in RNA editing of serotonin 2C receptors

“…Although it is known that the VGV isoform is less potent than the non-edited INI isoform, there is no consensus about the activity of other isoforms, despite many studies (Burns et al, 199 7 ; Fitzgerald et al, 1999; Herrick-Davis et al, 1999; Niswender et al, 1999; Wang et al, 2000a). We therefore reinvestigated the basal and 5-HT-stimulated activities of various isoforms.…”

“…Previous studies demonstrated that mRNA editing of 5-HT 2C R reduces receptor functions, including 5-HT potency, agonist binding affinity, constitutive activities, and G protein coupling activity (Burns et al, 1997; Fitzgerald et al, 1999; Niswender et al, 1999; Wang et al, 2000b; Berg et al, 2001; Gurevich et al, 2002b). The unedited INI isoform has the potency of the constitutive activity of the 5-HT 2C R, while its activity is inhibited proportionally to the extent of editing, with the fully edited VGV isoform displaying the lowest degree of receptor activity (Herrick-Davis et al, 1999; Niswender et al, 1999; Wang et al, 2000b).…”

“…Combinational editing at these five sites changes three amino acids (I156, N158, and I160) of the unedited receptor (INI), resulting in expression of 24 different editing isoforms in specific brain regions (Wang et al, 2000b; Nishikura, 2006; Werry et al, 2008). In vitro studies showed that RNA editing modulates receptor functions, including 5-HT potency, agonist binding affinity, constitutive activities and G protein coupling activity (Burns et al, 1997; Fitzgerald et al, 1999; Niswender et al, 1999; Wang et al, 2000b; Gurevich et al, 2002a), suggesting that RNA editing of 5-HT 2C R mRNA may modulate serotonergic systems in the brain that have causative relevance to neuropsychiatric disorders (Maas et al, 2006; Werry et al, 2008). Moreover, the extent of 5-HT 2C R mRNA editing that occurs in response to stress or the 5-HT selective reuptake inhibitor fluoxetine depends on the genetic background of mice (Englander et al, 2005).…”

RNA Editing Dynamically Rewrites the Cancer Code

“…A-to-I editing is very widespread in the human genome [4] and spans both coding and non-coding regions, mainly within highly repetitive Alu elements, which can form the requisite double-stranded structure for ADAR-mediated editing. RNA editing has been shown to create different protein isoforms [5], modulate alternative splicing [6], and regulate transcript stability by modifying microRNAs and microRNA binding sites [7,8]. In the context of cancer, as this recent work shows, RNA editing may serve as an additional, and much more dynamic and flexible, counterpart to genomic-level mutations.…”

Identification and relative quantification of adenosine to inosine editing in serotonin 2c receptor mRNA by CE

“…In the conditions described here, only the NE and E forms were not separated from each other. Setting up new conditions for separating them did not appear necessary to us because the E site has only a very low probability to be edited alone, the editing of other sites being a prerequisite to its own editing [1,6,12]. However, in case it would be necessary to separate the E from the NE form, this can be achieved by changing the parameters of the electrophoresis, but at the price of obtaining other unresolved forms (not shown).…”