A analysis group from The Hong Kong University of Science and Technology (HKUST) has made a breakthrough discovery in understanding the molecular equipment of RNA silencing. The group uncovered how the human enzyme DICER achieves extremely exact processing of microRNAs (miRNAs), advancing gene regulation analysis and providing new insights into the mechanisms underlying most cancers, immune issues, and genetic illnesses.
This examine, led by Prof. Tuan Anh NGUYEN, Associate Professor within the Division of Life Science at HKUST and collectively performed by his PhD college students Minh Khoa NGO and Cong Truc LE, has been revealed within the prestigious journal Nature underneath the title “DICER cleavage fidelity is governed by 5′-end binding pockets.“
The message of human life is encoded in our genomic DNA by way of transcription of messenger RNAs which carries and executes the genetic directions. RNA molecules, usually single-stranded and composed of ribonucleotides (A, U, G, and C), play important mobile roles starting from protein synthesis and gene regulation to serving as genetic materials in sure viruses. Within this RNA-based regulatory panorama, the enzyme DICER features as a extremely exact “molecular scissors.” It cleaves double-stranded RNA precursors into quick regulatory RNAs which can be subsequently included into the RNA-induced silencing advanced (RISC), enabling the cell to establish and suppress incorrect or pointless genetic messages-much like marking and deleting errors in a textual content.
For years, researchers have sought to know how DICER achieves its extraordinary cleavage accuracy. Using state-of-the-art biochemical and structural biology strategies and high-resolution cryoelectron microscopy (cryo-EM), the HKUST analysis group visualized DICER–RNA interactions at an atomic degree. The examine’s first creator Minh Khoa Ngo defined, “CryoEM allowed us to observe how RNA substrates engage with DICER at an atomic detail. These structural snapshots vividly reveal the dynamic adjustments DICER makes when processing different RNA sequences, fundamentally reshaping our understanding of how this enzyme functions.”
The group found that earlier than cleavage happens, DICER undergoes conformational changes that information RNA substrates into the right register. The enzyme then makes use of particular structural elements-particularly amino acids inside 5′-end binding pockets-to align the RNA exactly earlier than adopting the “cleavage ready” conformation.
Prof. Nguyen, the corresponding creator, elaborated: “It is as if the scissors can ‘read’ exactly where the RNA should be cut at single nucleotide resolution, ensuring the integrity of the entire message. Our study uncovers not only the previously known U-favoured 5′-end binding pocket, but also a newly identified G-favoured 5′-end binding pocket. Together, these form a dual-pocket mechanism that determines cleavage positioning, providing an entirely new framework for understanding how DICER accommodates and processes diverse RNA substrates.”
He additional added: “The importance of this discovery extends beyond basic biology. By revealing how DICER integrates 5′-end identity, RNA motifs, and domain motions to maintain cleavage fidelity, our findings lay a mechanistic foundation for improving RNA-based therapeutics, optimizing gene silencing technologies, and uncovering the molecular origins of DICER-related genetic diseases.”
Reference: Ngo MK, Le CT, Nguyen TA. DICER cleavage constancy is ruled by 5′-end binding pockets. Nature. 2026. doi: 10.1038/s41586-026-10211-5
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