Directional translocation resistance of Zika xrRNA

Nat Commun. 2020 Jul 27;11(1):3749. doi: 10.1038/s41467-020-17508-7.

Abstract

xrRNAs from flaviviruses survive in host cells because of their exceptional dichotomic response to the unfolding action of different enzymes. They can be unwound, and hence copied, by replicases, and yet can resist degradation by exonucleases. How the same stretch of xrRNA can encode such diverse responses is an open question. Here, by using atomistic models and translocation simulations, we uncover an elaborate and directional mechanism for how stress propagates when the two xrRNA ends, [Formula: see text] and [Formula: see text], are driven through a pore. Pulling the [Formula: see text] end, as done by replicases, elicits a progressive unfolding; pulling the [Formula: see text] end, as done by exonucleases, triggers a counterintuitive molecular tightening. Thus, in what appears to be a remarkable instance of intra-molecular tensegrity, the very pulling of the [Formula: see text] end is what boosts resistance to translocation and consequently to degradation. The uncovered mechanistic principle might be co-opted to design molecular meta-materials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Nucleic Acid Conformation
  • RNA Transport
  • RNA, Viral / chemistry
  • RNA, Viral / genetics
  • RNA, Viral / metabolism*
  • Stress, Mechanical
  • Thermodynamics
  • Zika Virus / genetics*

Substances

  • RNA, Viral