Zucko, Dora2023-04-132023-04-132023-01https://hdl.handle.net/11299/253714University of Minnesota Ph.D. dissertation. January 2023. Major: Veterinary Medicine. Advisor: Kathleen Boris-Lawrie. 1 computer file (PDF); viii, 213 pages.According to the central dogma, the main role of RNA is to carry vital information for protein synthesis (mRNA) or to support protein synthesis machinery (tRNA, rRNA, sn- and snoRNAs). However, the complex universe of post-transcriptional control has challenged that view, positing that the events occurring on the RNA once it’s synthesized have a multitude of functions to allow for proper gene expression. This dissertation examined the roles of three post-transcriptional regulatory processes in virus infection and cancer: non-coding RNAs, RNA modification and RNA-binding proteins. The objective of the first data manuscript was to investigate whether an abundance of publicly available RNA sequencing data can be repurposed to mine for new RNA species. Using computational prediction tools, I predicted how a class of non-coding RNAs, circular RNAs, may regulate host and viral mRNAs in two cohorts of HIV-1 infected patients. The objective of the second data manuscript was to examine how an unconventional biochemical mRNA modification, typically present on non-coding nuclear RNAs, impacts their engagement with canonical and non-canonical protein synthesis machinery in malignantly transformed canine cells. The objective of the third data manuscript was to identify mRNAs associated with an RNA-binding protein RNA helicase A (DHX9/RHA) which guides the non-canonical protein synthesis, and to assess the requirements needed for this interaction. A triad of molecular, biochemical and bioinformatic approach was employed to generate new knowledge in the field of RNA biology. These studies provide an amplitude of directions for future projects to explore; a new approach to host-pathogen interactions in response to HIV-1 infection or a novel mechanism of protein synthesis in cancer, with an overarching goal to increase the understanding of gene expression at the RNA level.enThesis or Dissertation