55.6 Thursday, Jan. 5 The squid nervous system expresses novel RNA editing enzymes ROSENTHAL, JJC*; CORREA, RA; PALAVICINI, JP; Institute of Neurobiology, Univ. of Puerto Rico/RCM; Institute of Neurobiology, Univ. of Puerto Rico/RCM; Institute of Neurobiology, Univ. of Puerto Rico/RCM email@example.com
Genome sequencing projects make it clear that an organism’s complexity is not proportional to the number of genes that it possesses. Accordingly, other mechanisms must be important to generate genetic diversity. RNA editing, used primarily in the nervous system, is one example. Among eumetazoans, adenosine deamination to inosine is the most common form of RNA editing, however the extent to which it is used to change codons varies greatly. Although it clearly has important consequences in vertebrates, it is infrequently used to modify protein structure. Recoding by A-to-I editing is much more common in invertebrates. For example, in Drosophila an order of magnitude more A-to-I recoding events than in mammals have been identified. In cephalopods, it is even more robust. In fact, more A-to-I recoding events have been uncovered in a handful of mRNAs from the squid nervous system than in the entire human transcriptome. What then are the underpinnings of high level editing in squid? We hypothesized that they have evolved specializations to their editing enzymes. Vertebrates have two ADARs, the enzymes that catalyze A-to-I editing: ADAR1 and ADAR2. Both contain a highly conserved catalytic domain and 2 or 3 double-stranded RNA binding domains (dsRBDs). Squid express an ortholog of each; however in both cases they have unique features. Squid ADAR1 contains a large serine rich domain with close to 70 potential phosphorylation sites that appears to be unique among ADARs. Squid ADAR2 contains an extra dsRBD. In addition, the mRNAs for both squid ADARs are themselves extensively edited, leading to a tremendous diversity of isoforms. In vitro assays using recombinant enzymes indicate that both the novel domains, and the self-editing, augment editing site recognition.