RNA editing of the serotonin 5HT2C receptor and its effects on cell signalling, pharmacology and brain function.
The process of RNA editing involves the modification of mRNA at specific sites by adenosine deaminases that act on RNA (ADAR) enzymes. By catalyzing the conversion of adenosine to inosine, these enzymes alter the way in which the mRNA is translated, and consequently alter the primary structure of the resultant proteins. The serotonin (5HT) 2C receptor (5HT2CR) is currently the only known member of the superfamily of seven transmembrane domain receptors (7TMRs) to undergo this modification, and provides a fascinating case study in the effects of such changes. Here we review the current state of knowledge surrounding the editing of the 5HT2CR, the stark differences in signalling arising due to this process, and the potential for (and difficulties in) exploiting the phenomenon for improved therapeutic intervention in various neurological disorders.
Drug Discovery Biology Laboratory, Department of Pharmacology, Monash University, Clayton, VIC 3800, Australia.
Tim D
TD
Werry
Richard
R
Loiacono
Patrick M
PM
Sexton
Arthur
A
Christopoulos
D000243:Adenosine Deaminase / Q000502:physiology; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D001523:Mental Disorders / Q000378:metabolism; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics / Q000502:physiology; D017393:RNA Editing; D016601:RNA-Binding Proteins; D044405:Receptor, Serotonin, 5-HT2C / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D044405:Receptor, Serotonin, 5-HT2C; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; D019204:GTP-Binding Proteins