Simulations illuminate the folding of the RNA genome of the Zika virus and other confined RNAs

What is it about?

Squeezing a string into a ball changes how it behaves: distant segments are forced into close contact, ends are more likely to meet, and movement in one region affects the rest. Similar principles apply to nucleic acid polymers, such as RNA, when inserted into virus particles or other small compartments, but there is no framework for modelling the effects of confinement on RNA folding. Here we develop such a framework, combining molecular dynamics simulations with experimental measurements of contacts within unconfined and confined RNA molecules. We find that confined RNA exhibits glassy and liquid crystalline behavior, and that genome circularization, a long-range interaction between the two ends of the viral RNA, is facilitated under confinement. This interaction controls whether the viral genome is translated into proteins or replicated.

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Photo by Alex Preusser on Unsplash

Photo by Alex Preusser on Unsplash

Why is it important?

Understanding how the RNA genome of the Zika virus is folded gives important insight into the virus because the contacts between different parts of the molecule, particularly the one connecting the two ends of the molecule, play a role in its ability to cause disease. More broadly, our model can be applied to other systems that involve confined RNA molecules, for example mRNA vaccines in which the RNA is encapsulated within a lipid nanoparticle.

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