The adenosine deaminase acting on RNA (ADAR) enzymes convert adenosine to inosine in double-stranded (ds)RNA. This RNA modification is known as A-to-I RNA editing. Inosine can be read as guanosine during translation so a different amino acid can be inserted at an edited position in a transcript. This type of RNA editing is catalyzed by ADAR2 and is known as site specific editing or recoding editing. It occurs on transcripts expressed in the central nervous system. In mammals most RNA editing is of transcripts encoding Alu elements. If a transcript encodes Alu elements in reverse orientation to each other, then they can base-pair and form an RNA duplex that can undergo RNA editing. This RNA editing is very important for innate immunity as inosine in transcripts helps the cell to distinguish the transcript as ‘self’ and not a foreign pathogen. ADAR1 is responsible for RNA editing of transcripts encoding Alu elements and if it is inhibited then this triggers an immune response which can lead to cell death. In Drosophila there is only one Adar enzyme that has properties of both mammalian ADAR1 and ADAR2. Drosophila Adar catalyzes site specific RNA editing at more that 1000 position in transcripts mainly expressed in the central nervous system. However, it is also involved in innate immunity in the flies. The project will focus on the regulation and RNA editing by ADAR proteins, both in mammals and in Drosophila. It will investigate whether ubiquitination of mammalian ADAR1 is an important regulatory mechanism for controlling ADAR1. It will also investigate the expression of Drosophila Adar by immunofluorescence.