Roles of the 3' Untranslated Region of a Positive Strand Viral RNA

Oregon State University, Corvallis OR

Investigators

Abstract

The genomes of positive strand RNA viruses are unique in that they serve both as messenger RNAs and as templates for genome replication. Regulatory regions that control and coordinate these competing uses of the same RNA mostly reside in the untranslated regions (UTRs) of the genomic RNA. Defining the properties of the UTRs is therefore crucial to understanding the infections of viral pathogens. This project investigates the roles of a unique plant viral 3'-UTR, the tRNA-like structure (TLS) of Turnip yellow mosaic virus (TYMV) RNA. The TYMV TLS can be valylated and binds the translation elongation factor eEF1A; these properties are essential for infection. Two recently discovered roles for the TYMV TLS are being studied in detail: (1) a role in supporting the translation or gene expression of the viral RNA, and (2) a role in negatively regulating the onset of genome replication (minus strand synthesis). The first role is being studied by identifying the extent to which RNA stability and translation enhancement contribute to efficient gene expression derived from the TLS. The detailed mechanism of translational enhancement is being studied with a variety of biochemical techniques aimed at identifying molecular communication between the 3'-TLS and the 5'-end of the RNA, where ribosomes initiate protein synthesis. Based on preliminary results, these studies will investigate a role for translation elongation factor eEF1A in enhancing the initiation of translation. eEF1A has also been shown to be capable of repressing minus strand synthesis, a repression that might be relieved during an infection as viral gene expression produces viral replication proteins that displace eEF1A from the TLS by competitive binding. This scenario will be investigated by testing whether eEF1A binding to the TLS is relieved when viral proteins are present. These studies will clarify the roles of a viral 3'-UTR in regulating and enhancing viral infection. This project will involve undergraduate and graduate students, providing a training experience for the next generation of scientists.