Poster abstracts

Poster number 115 submitted by Suba Rajendren

Molecular Mechanisms to Regulate RNA Editing in nervous system

Suba Rajendren (Genome, Cell and Developmental Biology Program, Indiana University School of Medicine, Bloomington, IN), Jack Townsend (Medical Sciences Program, Indiana University School of Medicine, Bloomington, IN), Heather A. Hundley (Medical Sciences Program, Indiana University School of Medicine, Bloomington, IN)

Abstract:
RNA editing alters genomically encoded information to generate the transcriptomic diversity required for normal development and proper neuronal function in all animals. Aberrant RNA editing is associated with neurological disorders and cancers in humans. The adenosine deaminase acting on RNA (ADAR) family of enzymes catalyzes adenosine (A) to inosine (I) RNA editing. The mechanisms that regulate ADAR specificity and editing efficiency are not well understood. Our lab utilizes Caenorhabditis elegans to study the cellular factors and molecular mechanisms which regulate RNA editing. We determined that ADR-2, the editing enzyme has reduced affinity for RNA. ADR-2 interacts with ADR-1, an editing-deficient member of the ADAR family, and substrate recognition is determined by this ADR-1/ADR-2 complex. However, in the nervous system, ADR-1 is not required for ADR-2 to edit certain targets, which have one or two highly-edited sites To begin to elucidate the neural specific regulation of editing in development, we performed high-throughput sequencing of RNA isolated neural cells from two different life stages of C. elegans (first stage larval (L1) and young adults). Differential gene expression analysis indicates that ~10,000 genes are developmentally regulated and 35% of them are dependent on the expression of ADR-2. De novo identification of editing sites indicates that L1 stage has ~ 10-fold higher number of sites than young adults, that are enriched for intronic where sites from young adults enriched for 3’-UTRs. Majority of the sites (62%) identified in young adults show increased level of editing than L1. We identify a group of genes, have only few editing sites (<5) and exhibit increased editing during development. This group includes genes where ADR-1 was previously shown to be not required foe editing. Interestingly, the ratio of ADR-2/ADR-1 is increased during development at the RNA level. We hypothesize that this regulation of ADR-2/ADR-1 ratio determines the substrate recognition mechanism and editing efficiency during development. Elucidating how ADR-2 binds to substrate mRNAs in specific tissues during development will result in identification of molecular mechanisms that regulate RNA editing.

Keywords: RNA editing, Nervous system