Werry Tim D, Loiacono Richard, Sexton Patrick M, Christopoulos Arthur
Drug Discovery Biology Laboratory, Department of Pharmacology, Monash University, Clayton, VIC 3800, Australia.
Pharmacol Ther. 2008 Jul;119(1):7-23. doi: 10.1016/j.pharmthera.2008.03.012. Epub 2008 May 2.
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.
RNA编辑过程涉及由作用于RNA的腺苷脱氨酶(ADAR)对特定位点的mRNA进行修饰。通过催化腺苷向肌苷的转化,这些酶改变了mRNA的翻译方式,从而改变了所产生蛋白质的一级结构。血清素(5HT)2C受体(5HT2CR)是目前已知的七跨膜结构域受体(7TMRs)超家族中唯一经历这种修饰的成员,并为这种变化的影响提供了一个引人入胜的案例研究。在这里,我们综述了围绕5HT2CR编辑的当前知识状态、由于这一过程而产生的信号传导方面的显著差异,以及利用这一现象改善各种神经疾病治疗干预的潜力(和困难)。