Grant: Project Grant

Circular RNAs (circRNAs) were originally identified in the seventies but were dismissed as splicing errors. The technology used to extract total RNA from the cells also missed identifying these circRNAs because they usually relied on techniques that identify the polyadenylated tails of the RNA molecules. Due to their inherent circularized structures, these circRNAs lacked tail ends and so were never identified. Newly developed RNA sequencing technologies have now re-discovered their abundance within the cells. Although the circRNAs are derived from protein-coding regions of the genome, they do not code for any proteins and are categorized as noncoding RNAs. Understanding their function and mechanism of action will delineate how these circRNAs can be used to treat human diseases such as cancer. Unfortunately, we do not have any methods to systematically query their function, let alone their role in any disease condition. To address this, we have developed a novel lentivirus-based library that can turn "OFF" every single circRNA in the genome. Using this, we screened human cancer cells and have now identified four circRNAs that are essential for the survival of these cells. Here we propose to extend our novel work to additional cancer types and identify which circRNAs are essential to maintain the cancer cell proliferation and explore their mode of action. Completion of our proposal will identify the circRNAs essential for cancer cells and the genes that they regulate leading to the development of a new generation of therapeutic strategies.