Viroid models to study evolution of RNA trafficking motifs for host adaptation

Ohio State University, The, Columbus OH

Investigators

Abstract

Infectious RNAs including viroids and viruses must traffic between cells in order to establish systemic infection. This project addresses the role of noncoding RNA structural motifs for trafficking in host adaptation. It tests the hypothesis that (i) an infectious RNA can rapidly evolve new three-dimensional (3D) motifs for trafficking as a means of host adaptation, and (ii) different infectious RNAs can evolve distinct trafficking motifs for adaptation to the same host. This hypothesis was developed from the following observations. First, when a particular motif, called loop 19, of Potato spindle tuber viroid (PSTVd) was obliterated to abolish trafficking (but not replication) in the experimental host plant Nicotiana benthamiana, a new loop (loop 19*) evolved to restore trafficking. Second, some viroids, such as Hop stunt viroid (HSVd), differ significantly in sequences from PSTVd but also can infect N. benthamiana systemically. To test this hypothesis, the following experiments will be performed: 1) to elucidate the 3D structure of loop 19 and determine whether loop 19* is similarly structured, 2) to determine the cellular boundary at which loop 19 and loop 19* function, and 3) to perform a genome-wide mutational identification of HSVd trafficking motifs and compare them with the PSTVd motifs that have already been identified for similarities and differences. This project will contribute new knowledge about the molecular mechanisms underlying the evolution of infectious RNAs and broadly the unifying and unique principles controlling the systemic trafficking of different RNAs. New research tools and experimental systems developed may also help transform research on the general principles of RNA structure-function relationships. This project will train undergraduate/graduate students in developing cutting-edge cross-disciplinary approaches to study fundamental biological problems, and help enhance science education for elementary/middle/high school students, including traditionally underrepresented groups.