A domestic research team has found clues needed to design ribonucleic acid (RNA) therapies more precisely.
The Ministry of Science and ICT said on the 11th that a joint team led by V. Narry Kim, Director General of the Institute for Basic Science (IBS) RNA Research Center, and Noh Seong-hun, a professor in the Department of Biological Sciences at Seoul National University, has for the first time identified the activation process of the protein "Argonaute," which regulates gene expression. The findings were published the same day in the international journal Nature.
Argonaute is a protein that seeks out and suppresses genetic information that is unnecessary or produced in excess inside cells. In this process, Argonaute binds to microRNA (miRNA) and locates the target messenger RNA (mRNA) to block its function. Simply put, miRNA serves as an address, and Argonaute follows that address to dial down gene activity.
Until now, the process by which miRNA binds to Argonaute to actually acquire gene-suppressing function had not been clearly understood. The researchers used cryo-electron microscopy to observe, at the atomic level, how Argonaute becomes activated.
The analysis found that a protein called a chaperone holds Argonaute in an open conformation to create space for miRNA to enter. A chaperone is an accessory protein that helps other proteins acquire their proper shape. When miRNA enters this space, the chaperone dissociates, and Argonaute shifts to a closed structure capable of gene regulation.
The team reproduced this process in vitro to check whether the assembled Argonaute complex properly cleaves the target mRNA. In particular, Argonaute operated stably only when double-stranded miRNA, the form that natively exists in cells, was present; when miRNA was absent or single-stranded, the normal structure did not form.
They also analyzed which RNAs bind well to Argonaute. The chemical properties of RNA, the double-helix structure, and a length of 20–24 nucleotides emerged as key conditions. The team also examined how chemical modifications in small interfering RNA (siRNA) therapies currently used in the clinic affect Argonaute assembly. siRNA is an artificial RNA that selectively reduces the activity of specific genes to prevent disease-causing proteins from being produced.
V. Narry Kim, Director General, said, "This research provides a molecular basis for RNA therapeutic design that had relied on experience." Professor Noh Seong-hun said, "It is meaningful that we directly observed not a finished structure, but the process by which a protein acquires its function."
References
Nature (2026), DOI: https://doi.org/10.1038/s41586-026-10640-2