3D confinement reshapes RNA folding and enhances circularization in the Zika virus.

Confinement of the 11 kb Zika virus genome in virions reshapes RNA folding, with genome circularization occurring more frequently and contact scaling differing from unconfined cells.

• Why it matters: RNA functions in confined spaces, but how spatial constraints change long-range folding and structure ensembles is unclear, limiting interpretation of proximity ligation contact maps.
• What they did: The authors integrate proximity ligation data into coarse-grained molecular dynamics simulations to reconstruct Zika RNA 3D structures, comparing folding in virions versus cells for the 11 kb genome.
• The result: Contact probability versus linear distance follows different scaling laws under confinement, and circularization is more frequent in both experiments and simulations, with stems and predicted pseudoknot topologies supporting a confinement-driven structural mechanism.

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