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Global RNA Structure Analysis of the Poliovirus Genome: Functional RNA Elements within the Open Reading Frame

  • Author(s): Burrill, Cecily Parrish
  • Advisor(s): Andino, Raul
  • et al.

The genomes of RNA viruses often contain RNA structures that are crucial for translation and RNA replication, and play additional roles in the viral replication cycle. For the picornavirus family member poliovirus, a number of functional RNA structures have been identified, but much of its genome, especially the open reading frame, has remained uncharacterized. We have now generated a global RNA structure map of the viral genome using a chemical probing approach that interrogates RNA structure with single-nucleotide resolution. In combination with orthogonal evolutionary analyses, we uncover several conserved RNA structures in the open reading frame of the viral genome. Further characterization of one such RNA structure, located in the region encoding the RNA-dependent RNA polymerase, 3Dpol, reveals a new functional RNA structure required for viral infectivity, which we name RNA Infectivity-required Structure (RIS). Disrupting this RNA structure with synonymous mutations that do not change the amino acid sequence demonstrates that it participates in several steps of viral infection. Disrupting RIS causes a transient delay in viral RNA replication. However, RIS mutant viruses display a minute plaque size and a temperature sensitive phenotype that cannot be explained by the defect in RNA synthesis. Strikingly, we find that RIS mutations dramatically decrease the infectivity of the packaged viral particles, leading to an altered ratio of packaged RNA to infectious units. We propose that the new viral RNA element identified here plays a central role in infectious particle production that is conserved across the human enterovirus C group.

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