Poster abstracts
Poster number 96 submitted by Ananya Mahapatra
The kinase GSK-3 is a novel regulator of ADR-1 RNA recognition in the C. elegans nervous system
Ananya Mahapatra (Genome, Cellular and Developmental Biology, Indiana University, Bloomington), Heather A. Hundley (Department of Biology, Indiana University, Bloomington)
Abstract:
Previously, we have identified a unique post transcriptional mechanism in which under starvation conditions, a double stranded RNA binding protein, ADR-1, binds the mRNA of the transcription factor pqm-1 specifically in the nervous system. PQM-1 is an important mediator of the insulin signaling pathway contributing to longevity and the stress response as well as promoting survival from hypoxia. The binding of ADR-1 pqm-1 also causes decreased expression of pqm-1 at the mRNA level in the nervous system. Decreased expression of the transcription factor further leads to decreased expression of the genes activated by pqm-1 in the nervous system as well as other tissues, suggesting the presence of inter-tissue signaling. Additionally, this neural specific regulation in the nervous system affects how animals respond in hypoxic conditions. However, the cellular factors and molecular signatures that cause this unique post transcriptional gene regulation of hypoxic survival were largely unknown. In these studies, an unbiased forward genetic screen was performed to identify the factors that can affect the post transcriptional regulatory mechanism in the nervous system. From the screening process, we have identified five unique regulators of this mechanism. Three out of these five candidates affect the post transcriptional mechanism by controlling ADR-1 binding to pqm-1. Using whole genome sequencing and variant identification, dsh-2 was identified as a potential regulator of the mechanism. On testing the mechanism by which DSH-2 affects ADR-1 binding, we identified kinase GSK-3 as the factor that is responsible for controlling ADR-1 binding to pqm-1.
Keywords: GSK-3, RNA recognition, C elegans