Epitranscriptomic RNA modifications
Virus-host interactions
Ph.D., University of Pennsylvania, Perelman School of Medicine
Post Doctoral, Duke University Medical Center, Department of Molecular Genetics and Microbiology
Genome sequence maps have guided and vastly expanded our understanding of virus-host interactions. However, the outcome of viral infections is subject to additional levels of regulation not directly encoded in the viral genome sequence per se. One example is epitranscriptomic RNA modifications, such as N6-methyladenosine (m6A), where covalent modifications added to individual nucleotides on RNA can regulate it's metabolism and function, mostly through the recruitment or dismissal of functional RNA binding proteins. We believe that viruses have evolved to enrich for RNA modifications that are beneficial to viral replication. Indeed, the RNA base methylation, m6A, can enhance the replication of diverse viruses including Human Immunodeficiency virus 1 (HIV-1), Influenza A virus (IAV), Adenovirus and many more. These observations have been further expanded to modifications on cytidine: where 5-methylcytidine (m5C) and N4-acetylcytidine (ac4C) can enhance, respectively, the translation and stability of HIV-1 transcripts. Modifications, including m6A and pseudouridine, can also prevent modified RNA from activating innate immune responses, as demonstrated on the recent mRNA-based SARS-CoV-2 vaccines. Thus, RNA modifications clearly impact viral infections. However, it remains unclear how modifications such as m5C and ac4C impact viruses other than HIV-1; while the mechanisms of modification-dependent regulation of RNA stability and immune evasion remains largely unclear. The Tsai lab aims to elucidate these unexplored areas of viral RNA modifications, and how they impact virus-host interactions, focusing on Influenza A virus, HIV-1, and Hepatitis B virus as our model systems of interest.