Poster number 93 submitted by Ananya Mahapatra
Characterizing the Role of ADARs in Regulating Insulin Signaling and Inter-Organ Communication
Ananya Mahapatra (Genome, Cellular and Developmental Biology, Indiana University), Heather A. Hundley (Department of Biology, Indiana University )
Communication between organs is a vital factor that affects several physiological processes and is important for proper homeostasis. A major way in which organs communicate with each other is through insulin signaling. Since the nervous system is a master regulator of inter-organ communication, insulin signaling within the nervous system has the potential to affect insulin signaling in other organs. Even though neural insulin signaling can affect other organs, the molecular mechanism involved in the inter-organ communication through insulin signaling is unknown. Novel mechanisms of insulin signaling regulation have been attributed to RNA binding proteins since these proteins can control post-transcriptional gene expression. However, how this occurs molecularly is unclear. These gaps in the field emphasize the need to explore mechanisms of neural gene regulation and inter-organ communication.
My long-term goal is to understand how RNA binding proteins (RBPs) regulate gene expression to impact inter-organ communication and how misregulation could lead to disease. My preliminary data demonstrates that RBPs called adenosine deaminases that act on RNA (ADARs) regulate insulin signaling in the nervous system, which subsequently regulates insulin signaling in other tissues. My research uses the model system C. elegans since ADARs are essential in mammals and insulin signaling is conserved in C. elegans. C. elegans has two ADAR proteins- ADR-1 and ADR-2. My preliminary studies show that compared to wildtype, adr-2 lacking animals show decreased expression of genes regulated by insulin signaling. Interestingly, in animals that express ADR-2 solely in the nervous system, gene expression is like wildtype, suggesting insulin signaling is regulated cell-nonautonomously. My studies also suggest that loss of ADR-2 causes aberrant binding of ADR-1, thus impacting insulin signaling. My initial experiments testing neural ADR-1 binding suggest that ADR-1 binds irld-24, an insulin-receptor L domain protein, specifically in the absence of ADR-2. My proposed model is that in the absence of ADR-2, ADR-1 binds irld-24 aberrantly in the nervous system, which is responsible for causing downregulation of downstream genes regulated by insulin signaling throughout the animal.
Keywords: ADARs, insulin signaling, nervous system