Abstract
Mechanical anisotropy is an essential property for many biomolecules to assume their structures, functions and applications, however, the mechanisms for their direction-dependent mechanical responses remain elusive. Herein, by using a single-molecule nanopore sensing technique, we explore the mechanisms of directional mechanical stability of the xrRNA1 RNA from ZIKA virus (ZIKV), which forms a complex ring-like architecture. We reveal extreme mechanical anisotropy in ZIKV xrRNA1 which highly depends on Mg2+ and the key tertiary interactions. The absence of Mg2+ and disruption of the key tertiary interactions strongly affect the structural integrity and attenuate mechanical anisotropy. The significance of ring structures in RNA mechanical anisotropy is further supported by steered molecular dynamics simulations in combination with force distribution analysis. We anticipate the ring structures can be used as key elements to build RNA-based nanostructures with controllable mechanical anisotropy for biomaterial and biomedical applications.
Highlights
Mechanical anisotropy is an essential property for many biomolecules to assume their structures, functions and applications, the mechanisms for their directiondependent mechanical responses remain elusive
To better understand how Mg2+ affect the overall structure and stability of ZIKA virus (ZIKV) xrRNA1, small-angle X-ray scattering (SAXS) and differential scanning calorimetry (DSC) experiments were performed
DSC experiments demonstrated that the cooperative unfolding of xrRNA1 highly depends on Mg2+ concentrations (Supplementary Fig. S3)
Summary
Mechanical anisotropy is an essential property for many biomolecules to assume their structures, functions and applications, the mechanisms for their directiondependent mechanical responses remain elusive. RNAs’ diverse roles in many cellular processes are dictated by their propensities to fold into stable three-dimensional structures driven by numerous tertiary interactions[1,2]. Recent crystal structures of xrRNAs from Murray Valley encephalitis virus (MVEV, xrRNA2)[13] and ZIKA virus (ZIKV, xrRNA1)[14] reveal a stable and compact RNA fold centered on a Various single-molecule force spectroscopy techniques, e.g., optical tweezers, magnetic tweezers and atomic force microscope have been successfully applied to study RNA mechanical unfolding[7,8,17]. Recent developments in single-molecule nanopore-sensing technology have allowed the unfolding and translocation of RNAs through biological pores in a defined direction to be observed with fine details[18,19,20]. The narrowest constriction of α-HL is 1.4 nm in the stem domain (Supplementary Fig. S1) and, it only allows the translocation of single-stranded nucleic acids, but folded nucleic acids must unfold to pass through the pore[21]
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