The identification of functional RNA secondary structures

Abstract

<p>This dissertation journals the development of an RNA secondary structure prediction pipeline which can be used to identify potentially functional RNA structures. Its development and utility is demonstrated on viral and human RNAs. We begin by characterizing the RNA folding potential of the human genome and creating the RNAStructuromeDB (which also serves as a repository for all results presented herein). Next, we develop a method known as ScanFold to home in on specific RNA structures which have evidence for functionality and demonstrate its ability to do so using the HIV-1 and Zika virus genomes as positive controls. Later we characterize the full extent of ScanFold results, finding a correlation between ScanFold predictions and experimentally derived RNA structure probing data (ultimately highlighting ScanFold’s ability to identify potentially functional RNA structures with >70% accuracy). We then use ScanFold to identify potentially novel functional RNA structures embedded in the human oncogene MYC’s mRNA, several Herpevirus genomes, and the SARS-CoV-2 genome.</p>