Poster abstracts
Poster number 5 submitted by Aaron Bruns
SnRK1 phosphorylates eIF4E/eIFiso4E to inhibit translation as a component of antiviral defense
Aaron N. Bruns (OSBP), Sizhun Li (The Ohio State Uninversity), David M. Bisaro (Department of Molecular Genetics, The Ohio State Uninversity)
Abstract:
SNF1 related kinase 1 (SnRK1) is a central sensor and regulator of energy homeostasis in plants. As the plant homologue of animal AMP-activated protein kinase (AMPK) and yeast sucrose non-fermenting kinase (SNF1), SnRK1 senses the ATP:AMP ratio in the cell, activating catabolic processes when energy levels are low while simultaneously inhibiting anabolic processes. We previously demonstrated that SnRK1 conditions an innate antiviral defense effective against DNA and RNA viruses, including geminiviruses and TMV. We also showed that the geminivirus pathogenicity proteins AL2 and L2 interact with and inactive SnRK1 as a counterdefense. However, because SnRK1 has a multitude of targets, the mechanism by which SnRK1 interferes with viral infectivity was elusive. We have now demonstrated that SnRK1 interacts with and phosphorylates the mRNA cap binding protein eukaryotic initiation factor 4E (eIF4E), and its plant specific homologue eIFiso4E, at two serine and threonine residues that are conserved throughout the plant kingdom as well as invertebrates and yeast. However, these sites are absent in vertebrate eIF4E homologues, suggesting distinct regulatory mechanisms. Furthermore, we discovered that eIF4E/iso4E phosphorylation by SnRK1 inhibits translation in vivo using both plant and complemented yeast systems. This is the first evidence that SnRK1 directly inhibits translation in plant cells. It also suggests that SnRK1 phosphorylation of eIF4E/iso4E is a host defense analogous to PKR-mediated phosphorylation of eIF2α in vertebrate cells. Many plant viruses, including geminiviruses, rely on cap-dependent host translation for protein synthesis. Thus, limiting translation initiation through SnRK1 phosphorylation of eIF4E/eIFiso4E can effectively impede virus spread. (Work in the Bisaro lab is supported by USDA/NIFA 2015-6703-22999, NSF MCB-1158262, and NSF IOS-1354636; A.N.B. was supported in part by training grant NIH T32-GM-086252.)
Keywords: SnRK1, eIF4E, Translation