Our paper on predicting the stability of RNA double helix structures was published in Nucleic Acids Research and featured on the cover of the issue.
A research group led by Professor Naoki Sugimoto, Director of the Frontier Institute for Biomolecular Engineering Research (FIBER) at Konan University, Research Assistant Professor Ghosh Saptarshi, and Associate Professor Shuntaro Takahashi have developed a highly accurate method to predict the stability of RNA duplex structures in cells. This research achievement has the potential to dramatically improve the efficacy of nucleic acid medicine, including RNAi therapy, the next-generation treatment for genetic diseases and viral infections. This research result was published in Nucleic Acids Research and featured on the cover of the issue.
RNA is a type of genetic material that exists in cells as a transmitter for the production of proteins from the genetic information in DNA. It also serves as the genome for viruses such as the new coronavirus. The molecular structure of RNA is a single linear chain of four types of nucleobases: adenine, uracil, guanine, and cytosine. Adenine and uracil, and guanine and cytosine can pair with each other. Therefore, RNA can form a double-stranded structure by base pairing. In living organisms such as cells, RNA duplex formation can regulate gene functions. In particular, RNA interference (RNAi), which was the subject of the 2006 Nobel Prize in Physiology or Medicine, is a mechanism for regulating gene expression in which short RNAs form duplexes with target RNAs, which are then degraded. Therefore, technologies that utilize RNAi to degrade the RNA of disease-causing genes or the RNA of viral genomes to treat diseases and infectious diseases are attracting attention as new pharmaceutical technologies.
It has been known that the ease of duplex formation is determined by the combination of base pairs, and a method for predicting this has been established. However, unlike solution environments such as NaCl-contained solution in which experiments are usually conducted, the intracellular biological environment is a thick solution environment with a high concentration of molecules. It has been challenging to predict the stability of the formation of duplexes in such a solution environment, so the design of RNA for RNAi therapeutics has been in a state of exploration.
In this study, the FIBER research group artificially reproduced the crowded environment inside a cell by using polyethylene glycol, a water-soluble polymer also used as a pharmaceutical additive. By analyzing the stability of RNA duplex formation in the adjusted artificial environment, we have succeeded in developing a new prediction method that can predict the stability of RNA duplex formation in cells. By using this method, the stability of RNA duplex formation in different intracellular environments such as the nucleus, nucleolus, and even cytoplasm of a cell can be accurately predicted. The results of this research are expected to dramatically improve the efficacy of nucleic acid drugs by designing them to match the cellular environment.
This research was published in Nucleic Acids Research and featured on the cover of the issue. We will continue to synthesize and analyze artificial molecules that control nucleic acid structures by sharing the results of this research with our overseas core members.
【Publication Issue of Nucleic Acids Research】
Link to the NAR magazine as follows.
【Published Articles】
“Nearest-neighbor parameters for the prediction of RNA duplex stability in diverse in vitro and cellular-like crowding conditions”
S. Ghosh, S. Takahashi, D. Banerjee, T. Ohyama, T. Endoh, H. Tateishi-Karimata, and N. Sugimoto, Nucleic Acids Res., 51, (2023) 4101-4111.
【Front Cover】
