How do animals make, use,
and destroy small RNAs?
In eukaryotes, small (20–30 nt) RNAs direct Argonaute proteins to silence complementary RNA targets. Different classes of small RNAs regulate host gene expression, fight viral infections, and silence selfish genetic elements. We use genetics in mice and flies and biochemical approaches to understand the biological role of small RNA-mediated gene regulation.
What determines RNA stability?
Splicing, polyadenylation, and translational efficiency contribute to the stability of an mRNA, but these processes alone cannot explain the ~1,000-fold range of cellular RNA half-lives. We conduct genetic screens to identify novel proteins involved in regulating RNA stability. Understanding the molecular mechanisms underlying RNA stability in cells will inform the development of RNA-based drugs; studying RNA turnover determinants may lead to the discovery of new therapeutic targets for treatment of human disease.
How are RNAs destroyed?
Current models for RNA decay are derived from steady-state genetic and biochemical data, but how the rates of different RNA decay steps are coordinated or regulated to achieve required biological outcomes is not well understood. Our lab uses experimental and computational quantitative approaches to provide a transcriptome-wide, time-resolved perspective of RNA turnover pathways in animals. We apply metabolic labeling and high-throughput sequencing to reveal how the kinetics of various RNA turnover steps and their regulation influence steady-state transcript levels.