Researchers reveal universal mechanisms of DNA and RNA abnormalities.

DNA and RNA, the two main types of DNA and building blocks of life, are vulnerable to environmental triggers, which can cause them to deform, bend or twist. These abnormalities can greatly affect gene regulation and protein function, but are extremely difficult to measure using conventional techniques.

Recently, a research team led by a physicist from City University of Hong Kong (CityU) accurately measured the change in DNA caused by salt, temperature change and stretching force. Their findings, published in Proceedings of the National Academy of Scienceshelp reveal the underlying global deformation mechanisms of DNA and RNA.

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

The success of the research lies in a precise measuring instrument called magnetic forceps (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 the magnetic tweezers experiment, a small magnetic bead is attached to a molecule of interest, and a magnetic field is applied to manipulate the position of the bead.

By measuring the movement of the bead, researchers can study the mechanical properties of the molecule, such as its elasticity, toughness and response to an external force. This can be used to measure small changes in DNA and RNA evolution caused by environmental stimuli. Even small changes can accumulate along a long DNA or RNA molecule and cause a significant turnover of the DNA or RNA end.

In the experiments, the team used magnetic tweezers to accurately measure changes in DNA and RNA twist caused by salt, temperature change, and stretching.

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

For DNA, environmental stimuli usually modify the diameter of the DNA first, and then cause a tortuous change through strong coupling between DNA evolution and diameter. But for RNA, lowering the salt concentration or increasing the temperature “untie” the RNA because this widens the width of the RNA major groove and causes a decrease in twist. Hence, this is called a groove twisted coupling.

By analyzing data from other studies on protein binding, the team found that DNA and RNA follow the same common pathways when deformation occurs by protein binding, suggesting that the two pathways are used to reduce the energy cost of deforming DNA and RNA to facilitate protein facilitation. link.

Their findings indicate that the physical principles underlying DNA 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 the packing of DNA into cells and the related deformation energy cost,” he said. “The results also provide insight into how proteins recognize DNA and RNA and trigger deformations, which are essential steps in gene expression and regulation.” . Professor Dai Liang, associate professor in the Department of Physics at CityU, who co-led the research.

The first authors of the study are Tian Fujia, from CityU, and Zhang Chen and Zhou Ershi, from Wuhan University. Corresponding authors are Professor Dai, from CityU, and Professor Zhang Xinghua, from Wuhan University.