Exploring the dynamics of A-to-I editing in the mammalian brain

Abstract

Adenosine-to-Inosine RNA editing (A-to-I editing) has evolved as an important process for generating transcript diversity in metazoans. Several editing events which effect transcripts encoding proteins important for CNS function appear to be conserved in mammals, however the precise role these RNA editing events play in regulating physiology and behavior are not clear. The major goal of this work is to identify circumstances that lead to dynamic variations in the expression of different edited transcript isoforms within the mammalian brain in order to gain insights about the regulation and function of A-to-I editing in mammals. The results of these studies challenge popular models of dynamic editing at transcripts encoding 5HT2C receptors while providing new information about conserved global and context dependent patterns of A-to-I editing at various substrates in the mammalian brain. Furthermore, this work evaluates the roles of RNA processing of 5HT2C transcripts in the human genetic disorder Prader-Willi Syndrome (PWS).