SARS-CoV-2 RNA-Dependent RNA Polymerase Proteomics and Interactions with RNA-Binding FUS Protein

Abstract

The SARS-CoV-2 (COVID-19) pandemic will forever be a staple of the 2020s, with countries shutting down across the world and catalyzing revolutions in biochemical engineering. However, the virus itself is a distant echo of the SARS-CoV-1 (SARS) epidemic from the early 2000s - all three of which being of the same family and genus of betacoronaviruses. The trend of coronavirus outbreaks prompted the study of the similarities between SARS and COVID-19 while also investigating the proliferation of coronaviruses. This paper studied the changes in the RNAdependent RNA polymerase (RdRp), used in betacoronaviruses for gene expression and RNA genome replication, between SARS and COVID-19. Furthermore, proteomic studies were performed between strains of COVID-19 from across the world. Along with proteomics, the effect of FUS protein, a transcription factor that recruits and promotes RNA Polymerase II activity, was observed in transcription experiments with COVID-19 RdRp. Overall, the comparison between SARS and COVID-19 RdRp demonstrates a highly conserved structure and sequence - the uneven distribution of amino acid changes also suggests regions of the RdRp are conserved to maintain function. There were few mutations in the RdRp among COVID-19 strains compared to other proteins signifying a low rate of nonfatal mutations occurring. Lastly, the transcription assays with RdRp and FUS showed limited promotion of RdRp transcription with the addition of FUS, which may offer clues to COVID-19 taking advantage of other cellular machinery for proliferation and gene expression.