The origin of different bending stiffness between double-stranded RNA and DNA revealed by magnetic tweezers and simulations

The subtle differences in the chemical str uct ures of double-stranded (ds) RNA and DNA lead to significant variations in their biological roles and medical implications, largely due to their distinct bioph y sical properties, such as bending stiffness. Although it is well known that A-form dsRNA is stiffer than B-form dsDNA under physiological salt conditions, the underlying cause of this difference remains unclear. In this study, we employ high-precision magnetic-tw eez er e xperiments along with molecular dynamics simulations and re v eal that the relativ e bending stiffness betw een dsRNA and dsDNA is primarily determined by the str uct ure- and salt-concentration-dependent ion distribution around their helical str uct ures. At near-ph y siological salt conditions, dsRNA sho ws a sparser ion distribution surrounding its phosphate groups compared to dsDNA, causing its greater stiffness. Ho w e v er, at v ery high mono v alent salt concentrations, phosphate groups in both dsRNA and dsDNA become fully neutralized b y e x cess ions, resulting in a similar intrinsic bending persistence length of appro ximately 39 nm. T his similarity in intrinsic bending stiffness of dsRNA and dsDNA is coupled to the analogous fluctuations in their total groo v e widths and further coupled to the similar fluctuation of base-pair inclination, despite their distinct A-form and B-form helical str uct ures. © The Author(s) 2024.