Natural Variation in XRN1 and its Role in Determining Antiviral Specificity

Faculty Mentor Information

Paul A. Rowley

Abstract

XRN1 degrades uncapped cellular RNAs as part of RNA metabolism. Since viral RNAs are also uncapped, XRN1 can act as an antiviral defense mechanism. In this project, we examined the effectiveness and specificity of XRN1 to recognize and destroy double-stranded RNA viruses. Specifically, we wish to determine how natural genetic variation within species can affect host-virus interaction. We have identified and cloned polymorphic XRN1 from six different strains of Saccharomyces cerevisiae. We then tested their antiviral activities against viruses using a plate based assay to determine the loss of virus in response to the antiviral activity of polymorphic XRN1 genes. Results indicate that the capacity of XRN1 to destroy viruses is affected by natural genetic variation within the tested six strains. Further examination into the specificity of XRN1 will help to understand how XRN1 interacts with specific viruses and how XRN1 can maintain its essential housekeeping functions in addition to its antiviral activity.

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Natural Variation in XRN1 and its Role in Determining Antiviral Specificity

XRN1 degrades uncapped cellular RNAs as part of RNA metabolism. Since viral RNAs are also uncapped, XRN1 can act as an antiviral defense mechanism. In this project, we examined the effectiveness and specificity of XRN1 to recognize and destroy double-stranded RNA viruses. Specifically, we wish to determine how natural genetic variation within species can affect host-virus interaction. We have identified and cloned polymorphic XRN1 from six different strains of Saccharomyces cerevisiae. We then tested their antiviral activities against viruses using a plate based assay to determine the loss of virus in response to the antiviral activity of polymorphic XRN1 genes. Results indicate that the capacity of XRN1 to destroy viruses is affected by natural genetic variation within the tested six strains. Further examination into the specificity of XRN1 will help to understand how XRN1 interacts with specific viruses and how XRN1 can maintain its essential housekeeping functions in addition to its antiviral activity.