How basic processes in individual cells are integrated at the organismal level to control development and behavior is a major question in current biology. RNA replication and trafficking are emerging as a new paradigm to develop an understanding of the biological principles that integrate systemic gene regulation, viral infection, cellular antiviral responses, and basic mechanisms of cell-to-cell communication. This project addresses the fundamental and yet poorly understood question of how an RNA is replicated by the nuclear machinery and is further selected for transport into neighboring cells and distant organs in a plant, by using Potato spindle tuber viroid (PSTVd) as a highly tractable model. This small (359 nucleotides) infectious RNA has the capacity to replicate in the nucleus and traffic between cells and organs to establish infection. Because it does not have protein-coding capacity and helper viruses, this RNA must have evolved distinct structural motifs to exploit preexisting cellular machineries to accomplish replication and trafficking. Using a combination of biochemical, cellular, genetic, molecular and virological approaches, this project will (1) investigate the PSTVd RNA motifs that play specific roles in replication, (2) isolate and characterize the role of a cellular factor, RNA ligase, in replication, and (3) dissect the RNA motifs that mediate trafficking between specific cells. Results from the project are expected to provide new insights about how an infectious RNA utilizes the host cellular machinery to establish infection, and to help develop a conceptual framework for further studies on the mechanisms and functions of RNA replication and trafficking underlying many biological processes. This project will also train undergraduate/graduate students and postdoctoral fellows in developing cutting-edge multidisciplinary approaches to address fundamental biological problems in great depth and breadth.
