Universality in RNA and DNA deformations induced by salt, temperature change, stretching force, and protein binding

Abstract

Nucleic acid deformations play important roles in many biological processes. The physical understanding of nucleic acid deformation by environmental stimuli is limited due to the challenge in the precise measurement of RNA and DNA deformations and the complexity of interactions in RNA and DNA. Magnetic tweezers experiments provide an excellent opportunity to precisely measure DNA and RNA twist changes induced by environmental stimuli. In this work, we applied magnetic tweezers to measure double-stranded RNA twist changes induced by salt and temperature changes. We observed RNA unwinds when lowering salt concentration, or increasing temperature. Our molecular dynamics simulations revealed the mechanism: lowering salt concentration or increasing temperature enlarges RNA major groove width, which causes twist decrease through twist-groove coupling. Combining these results with previous results, we found some universality in RNA and DNA deformations induced by three different stimuli: salt change, temperature, and stretching force. For RNA, these stimuli first modify the major groove width, which is transduced into twist change through twist-groove coupling. For DNA, these stimuli first modify diameter, which is transduced into twist change through twist-diameter coupling. Twist-groove coupling and twist-diameter coupling appear to be utilized by protein binding to reduce DNA and RNA deformation energy cost upon protein binding.

Temperature-Dependent Twist of Double-Stranded RNA Probed by Magnetic Tweezer Experiments and Molecular Dynamics Simulations

“…We note that the MT measurements are Relation to Previous Work. The discrepancy between the thermally induced changes of dsRNA twist measured by MT and inferred from MD simulations that we present here can be contrasted with the results of a recent study of Tian et al, 25 where the authors report quantitative agreement between MT measurements and MD simulations. While their MT measurement agrees quantitatively with ours, the MD-derived twist changes differ.…”

“…The RNA version of the duplex has a sequence where U replaces T in both strands, and the hybrid sequence was obtained by replacing T by U in the complementary strand only. We also simulated a 25 bp RNA oligomer of the sequence CGACU CUACG GAAGG GCAUC UGCGC employed in earlier works. , …”

“…We also simulated a 25 bp RNA oligomer of the sequence CGACU CUACG GAAGG GCAUC UGCGC employed in earlier works. 24,25 We performed unrestrained atomic-resolution MD simulations with explicitly represented water molecules and ions using the Amber17 suite of programs. Each system was simulated at 7, 17, 27, 37, and 47 °C.…”

Effect of temperature on anisotropic bending elasticity of dsRNA: an all-atom molecular dynamics simulation

“…In the current simulations, we selected the initial A-type dsRNA with a 16 bp sequence of 5′-GCGC AAUG GAGU ACGC-3′, which has been used in the previous works. 41,42 Our all-atom MD simulations are similar to those in previous studies, 21,43,44 and we only briefly describe the content involved in the current simulations. We constructed the initial structure file of the RNA using the UCSF Chimera 1.15 software application, 45 as shown in Fig.…”

Biocontrol Potential of Sodin 5, Type 1 Ribosome-Inactivating Protein from Salsola soda L. Seeds

“…A possible explanation for the lower enzymatic activity of sodin 5 in the presence of NaCl could be due to the structural changes in the DNA substrate [ 67 ]. It is known that monovalent ions such as Na + stabilize DNA molecules interacting with phosphates and the grooves, altering the intramolecular fluctuations, which could be useful for enzyme-substrate interactions [ 68 ].…”