Transitions: Adopting a Protein Biochemistry Approach to Mechanistic Understanding of RNA Buffering

University Of Utah, Salt Lake City UT

Investigators

Abstract

This project will investigate a novel regulatory mechanism called RNA buffering that maintains messenger RNAs (mRNA) at stable abundances despite changes in their rates of synthesis and decay. Traditionally, mRNA abundances are thought to depend primarily on the strength of synthesis (transcription) with a minor influence of decay, but the mechanism and impact of dynamic RNA buffering on gene expression is unclear. RNA buffering was discovered in yeast and has only recently been demonstrated in multicellular organisms. This project will investigate RNA buffering in the plant model Arabidopsis thaliana. Studying this phenomenon is important because it challenges conventional views of how gene expression is regulated, and because its prevalence is not known. The resulting knowledge could help advance biotechnology (e.g., RNA buffering might interfere with strategies to manipulate gene expression, such as engineering crop resistance or production of pharmaceuticals). This project will also offer training opportunities to undergraduates, and yield new educational materials on RNA biology for students at the University of Utah and Salt Lake Community college, and for an online platform (learn.genetics). To discover how mRNAs are selected for RNA buffering, and how cells coordinate changes in transcription and decay rates that involve communication between the nucleus and cytoplasm, this project will explore the protein-protein and protein-RNA interactions involved. Genetic and biochemical experiments will be performed to identify and characterize proteins that interact with mRNA decay components implicated in RNA buffering (e.g., VARICOSE protein), and candidates will be tested and validated for their roles in RNA buffering through loss-of-function mutational studies. In addition to research outcomes, the project will also develop instructional materials on RNA biology for the learn.genetics platform that is a widely used resource for education by schools and the broader community. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.