Multivalent Cations Reverse the Twist-Stretch Coupling of RNA.

When stretched, both DNA and RNA duplexes change their twist angles through twist-stretch coupling. The coupling is negative for DNA but positive for RNA, which is not yet completely understood. Here, our magnetic tweezers experiments show that the coupling of RNA reverses from positive to negative by multivalent cations. Combining with the previously reported tension-induced negative-to-positive coupling reversal of DNA, we propose a unified mechanism of the couplings of both RNA and DNA based on molecular dynamics simulations. Two deformation pathways are competing when stretched: shrinking the radius causes positive couplings but widening the major groove causes negative couplings. For RNA whose major groove is clamped by multivalent cations and canonical DNA, their radii shrink when stretched, thus exhibiting positive couplings. For elongated DNA whose radius already shrinks to the minimum and canonical RNA, their major grooves are widened when stretched, thus exhibiting negative couplings.

Cytosine Methylation Enhances DNA Condensation Revealed by Equilibrium Measurements Using Magnetic Tweezers.

CpG methylation of DNA is common in mammalian cells. In sperm, the DNA has the highest level of CpG methylation and is condensed into toroidal structures. How CpG methylation affects DNA structures and interactions is important to understand its biological roles but is largely unknown. Using an RNA-DNA-RNA structure, we observed the equilibrium hopping dynamics between the condensed and extended states of DNA in the presence of polyamines or polylysine peptide as a reduced model of histone tails. Combing with the measured DNA elasticities, we report that CpG methylation of each cytosine nucleotide substantially increases DNA-DNA attraction by up to 0.2 kBT. For the DNA with 57% GC content, the relative increase caused by CpG methylation is up to 32% for the spermine-induced DNA-DNA attraction and up to 9% for the polylysine-induced DNA-DNA attraction. These findings help us to evaluate the energetic contributions of CpG methylation in sperm development and chromatin regulation.

Opposite Effects of High-Valent Cations on the Elasticities of DNA and RNA Duplexes Revealed by Magnetic Tweezers.

We report that trivalent cobalt hexammine cations decrease the persistence length, stretching modulus, helical density, and size of plectonemes formed under torque of DNA but increase those of RNA. Divalent magnesium cations, however, decrease the persistence lengths, contour lengths, and sizes of plectonemes while increasing the helical densities of both DNA and RNA. The experimental results are explained by different binding modes of the cations on DNA and RNA in our all-atom molecular dynamics simulations. The significant variations of the helical densities and structures of DNA and RNA duplexes induced by high-valent cations may affect interactions of the duplexes with proteins.