Inhibition of RNAi by Cell Death Signaling

University Of Missouri-Columbia, Columbia MO

Investigators

Abstract

The completion of this project will address unexplored aspects of the RNA interference (RNAi) gene silencing process. In preliminary experiments, it was discovered that cell death produces a signal to adjacent cells that inhibits RNA interference. The research will involve a characterization of modifier mutations that increase or decrease the magnitude of this signaling. The modifier collection will be examined for their effect on the molecular block of RNAi that occurs at the conversion of double stranded RNA to small interfering RNAs. By precise genetic and cytological localization of the mutations recovered, eventually to the single gene level, insight into the molecular basis of the signaling will be revealed by the identification of the corresponding genes involved. Secondly, because cell death signaling increases the expression of retrotransposons, a test of whether novel insertions occur at a greater frequency in conjunction with chronic cell death than in control conditions will be performed. Broader Impacts: Gaining insight in the mechanism of inhibition of RNA interference by cell death signaling will reveal the impact of cell death on viral resistance, transposable element and endogenous gene expression and any consequent impact on mutation rate due to new retrotransposon insertions. RNAi as a reverse genetic tool is impacted by its inhibition by cell death signaling. Thus, an understanding of this process has implications for the basic and applied use of RNAi because its effectiveness could be compromised under such circumstances. The modifier mutation characterization and transposon insertion projects will be conducted by a diverse set of undergraduates so that they will gain a practical appreciation for the principles of classical and modern genetics and potentially be inspired to pursue postgraduate careers. The postdoctoral associate on the project will gain experience in mentoring undergraduates.