Poster abstracts

Poster number 28 submitted by Chelsea Hull

Investigation of innate immune function by oxidation of age-related RNAs

Chelsea M. Hull (Chemistry and Center for RNA Molecular Biology, Pennsylvania State University), Saikat Ghosh (Chemistry and Center for RNA Molecular Biology, Pennsylvania State University), Zeynep Koc (Chemistry and Center for RNA Molecular Biology, Pennsylvania State University), Philip C. Bevilacqua (Chemistry and Center for RNA Molecular Biology, Pennsylvania State University)

Abstract:
The RNA-activated protein kinase, PKR is an RNA-binding protein and an essential sensor in the innate immune response. Upon binding of RNA, PKR can dimerize and undergo autophosphorylation, followed by phosphorylating eIF2alpha, which leads to termination of translation and eventually apoptosis. PKR has a well- characterized role in recognizing viral RNA and initiating the immune response in order to rid the virus. PKR is known to bind long stretches (>33 bp) of double-stranded RNA (dsRNA) non-sequence specifically, but recently has been shown to be more permissive, binding other functional, biological and non-conventional RNAs, as well as some proteins. The hypothesis is that PKR binds novel RNAs in vivo and a subset of them are oxidatively damaged, which leads to the known upregulation of PKR in age-related diseases. Many biological RNAs are prone to oxidative damage and this leads to diseases. Because of the known upregulation of PKR in cells of patients affected with age-related diseases, specifically Alzheimer’s disease (AD) and Parkinson’s disease (PD), there is potential that PKR interacts with RNAs that lead to these diseases. Cells affected with these diseases have stressed environments, partially due to reactive oxidative species produced by some of the disease-related proteins. There is an overall relation between innate immunity (PKR), oxidative stress and age-related diseases and my goal is to develop a mechanistic and molecular understanding of these phenomena. An investigation of PKR activation by a wide variety of RNAs including those related to AD is being performed under normal conditions and after the RNAs have been oxidatively damaged (by multiple methods) and I will present my recent results.

Keywords: Alzheimers Disease, PKR, RNA binding protein