A Universal Mechanism of DNA and RNA Deformation Identified

DNA and RNA, the two main types of nucleic acid and the building blocks of life, are susceptible to environmental stimuli, which can cause them to deform, bend or twist. These deformations can significantly affect gene regulation and protein functions, but they are extremely difficult to measure using traditional techniques. Recently, a research team co-led by a physicist from City University of Hong Kong (CityU) accurately measured the change in a nucleic acid induced by salt, temperature change and stretching force. Their findings help reveal the underlying universal deformation mechanisms of DNA and RNA.

While DNA and RNA deformations are of great biological importance, our understanding of them is limited due to the challenge of making precise measurements of nucleic acid deformations and the complexity of nucleic acid interactions. To overcome these two difficulties, a research team led by scientists from CityU and Wuhan University used a combination of experiments, simulations and theories to investigate the universality of DNA and RNA deformations.

The success of the research lies in an accurate measuring tool, called magnetic tweezers (MT). This is a powerful experimental technique used in biophysics and molecular biology to study the mechanical properties of biological molecules, such as DNA, RNA and proteins. In a magnetic tweezers experiment, a tiny magnetic bead is attached to a molecule of interest, and a magnetic field is applied to manipulate the position of the bead.

Through the experiments, the team quantified the DNA twist-diameter coupling constant and the RNA twist-groove coupling constant and applied the coupling constants to explain DNA and RNA deformations. By combining these findings with simulations, theory and other previous research results, the team found that the DNA and RNA deformation mechanisms induced by salt, temperature change and stretching force are driven by two common pathways: twist-diameter coupling for DNA and twist-groove coupling for RNA.

Their findings suggest that the physical principles underlying nucleic acid deformation are universal and can be applied to different types of nucleic acids and environmental stimuli.

“The latest findings can be applied to better understand DNA packaging in cells and the related deformation energy cost. The results also provide insights into how proteins recognize DNA and RNA and induce deformations, which are the key steps in gene expression and regulation,” said Professor Dai Liang, Associate Professor in the Department of Physics at CityU, who co-led the research.

Reference: Tian FJ, Zhang C, Zhou E, et al. Universality in RNA and DNA deformations induced by salt, temperature change, stretching force, and protein binding. Proc Natl Acad Sci USA. 2023;120(20):e2218425120. doi: 10.1073/pnas.2218425120

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