Poster abstracts

Poster number 64 submitted by Rebecca Toroney

PKR Activation by Stem-loop RNAs is 5’-Triphosphate Dependent

Subba Rao Nallagatla (Department of Chemistry, The Pennsylvania State University), Jungwook Hwang (Integrative Biosciences (IBIOS), The Pennsylvania State University), Rebecca Toroney (Department of Chemistry, The Pennsylvania State University), Xiaofeng Zheng (Department of Biochemistry and Molecular Biology, Life Sciences College, Peking University), Craig, E. Cameron (Integrative Biosciences (IBIOS) and Department of Biochemistry and Molecular Biology, The Pennsylvania State University), Philip C. Bevilacqua (Department of Chemistry, The Pennsylvania State University)

Abstract:
The protein kinase PKR is an interferon-induced enzyme in the innate immune system. In response to foreign RNA, PKR undergoes autophosphorylation and phosphorylates eIF2?, which inhibits translation initiation. While long stretches of double-stranded RNA activate PKR, certain transcripts containing imperfections and single-stranded regions can also activate it. We report that single-stranded (ss) RNAs with limited secondary structure activate PKR in a 5’-triphosphate-dependent fashion in vitro and in vivo. Moreover, ssRNAs with cellular 5’-end signatures, such as 7-methyl-guanosine or monophosphate, do not activate PKR. We demonstrate that PKR activation works independent of RIG-I and that interferon-± treatment enhances PKR’s ability to sense 5’-triphoshorylated ssRNA. These findings suggest that PKR surveillance of molecular features at the 5’-end of RNA presents a checkpoint in innate immunity.

Keywords: PKR, 5-triphosphate