RT Journal Article SR Electronic T1 Directional translocation resistance of Zika xrRNA JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.06.17.157297 DO 10.1101/2020.06.17.157297 A1 Antonio Suma A1 Lucia Coronel A1 Giovanni Bussi A1 Cristian Micheletti YR 2020 UL http://biorxiv.org/content/early/2020/06/18/2020.06.17.157297.abstract AB xrRNAs from flaviviruses survive in host cells for 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, 5′ and 3′, are driven through a pore. Pulling the 3′ end, as done by replicases, elicits a progressive unfolding; pulling the 5′ 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 5′ end is what boosts resistance to translocation and consequently to degradation. The uncovered mechanistic principle might be co-opted to design molecular meta-materials.Competing Interest StatementThe authors have declared no competing interest.