CAREER: Dissecting the Biogenesis and Function of Circular RNA in Simple Eukaryotes

Stanford University, Stanford CA

Investigators

Abstract

This project will study the function of circular RNA, a type of RNA recently discovered to be common to cells across the tree of life. The basic DNA instructions for life are shared among plants, animals and even simpler organisms, as is the basic way DNA is processed into RNA, the functional code of instructions for all cells. Only very recently, a new feature of this process was discovered: copies of DNA can be processed into circular RNA molecules, which are sometimes remarkably abundant in cells, and have features that suggest they have important functions. Research into circular RNA will benefit the public by increasing scientific knowledge of basic mechanisms of genome evolution and function. The research will be disseminated to the public through seminars, publications and by directly integrating the research projects with educational programs aimed at high school, undergraduate and graduate students with a focus on groups that have traditionally been underrepresented in science. In addition, the integration of experimental, statistical and computational approaches in this research will serve as a template for development of a core class aimed at graduate students to teach the principles of statistics to biologists and the principles of biology to statistically trained students. Circular RNA is a novel class of RNA in different organisms. It is likely to be generated in a pathway linked to RNA splicing, suggesting tha suggests that splicing may have functions apart from excising introns to generate mature mRNAs that code for protein. Compared to other classes of expressed RNA, circular RNA has been the subject of little attention and study. This project will directly investigate circular RNA in unicellular eukaryotes where RNA processing is known to be complex and play important functional roles. Using the opportunities provided by recent technological advances in sequencing, the project will entail developing novel statistical and computational approaches coupled with new experimental designs to increase the understanding of circular RNA biogenesis and function. The statistical, computational and experimental methods develop in this project will be generally applicable to studying circular RNA across a variety of unicellular and multicellular organisms. This award is co-funded by the Genetic Mechanisms Program in the Division of Molecular and Cellular Biosciences and the Division of Emerging Frontiers in the Biological Sciences Directorate, and by the Statistics Program in the Division of Mathematical Sciences in the Mathematical and Physical Sciences Directorate.