Nature, a science journal with an acceptance rate of only 8%, published an article on 3/3 titled "DICER cleavage fidelity is governed by 5′-end binding pockets." This groundbreaking work was carried out by two PhD students, Ngo Minh Khoa and Le Cong Truc, under the guidance of Associate Professor Nguyen Tuan Anh from the School of Science, Hong Kong University of Science and Technology (HKUST).

The research focused on deciphering the biosynthesis of thousands of microRNA (microRNA) molecules in cells. For two decades, scientists believed the DICER enzyme, which acts as a "biological scissor" to cleave precursor miRNA into small fragments and initiate gene silencing, had only one "recognition pocket" to determine the cleavage site. This pocket recognized three types of ribonucleotides: A, U, C, but notably missed G. Associate Professor Tuan Anh considered this a significant gap in biological logic, as natural RNA contains all four types.

G binding pocket (sky blue) and U binding pocket (green) identified through cryo-electron microscopy (cryo-EM). *Image provided by subjects*

The team's breakthrough revealed that DICER actually possesses a "second pocket" specifically designed to recognize G. They achieved this by combining biochemical methods, which Tuan Anh's laboratory had refined over 9 years, with advanced cryo-electron microscopy (cryo-EM) technology.

Ngo Minh Khoa, the article's first author, explained that cryo-EM allowed them to visualize how RNA binds to DICER at an atomic level. Le Cong Truc added that applying bioinformatics to analyze large datasets from complex biochemical experiments was a key factor in quickly deciphering DICER's mechanism. Khoa noted, "This enzyme can change its shape much more flexibly than scientists previously knew."

Associate Professor Kwon Sung-Chul, an RNA expert at the School of Medicine, University of Hong Kong, emphasized the importance of this discovery. He stated that deciphering DICER's structure and mechanism across diverse substrates fills a 20-year gap in molecular biology. This research also opens new avenues for therapeutic treatments, particularly for cancer, based on RNA interference (RNAi) mechanisms.

Associate Professor Tuan Anh acknowledged that venturing into cryo-EM research to directly observe DICER's 3D structure was a risky endeavor. The team faced numerous costly failures. For instance, lacking specialized computers, PhD students often worked through the night, "borrowing" machines from other laboratories.

After more than three years of diligent work, the team finally received Nature's acceptance. This achievement fulfilled Associate Professor Tuan Anh's long-held aspiration since starting his teaching career. He firmly believes, "I always believe that Vietnamese intellect is fully capable of competing fairly with international peers in experimental science, if given the right opportunities and guidance."

Associate Professor Nguyen Tuan Anh (front row, center) with PhD students Ngo Minh Khoa (back row, far right) and Le Cong Truc (next to Khoa). *Image provided by subjects*

Associate Professor Tuan Anh has a notable publication record, including two previous articles in Cell, a world-leading biology journal. One of his studies was voted among the top 10 events of 2015 by the Korean Federation of Science and Technology Societies (KOFST). At HKUST, he has mentored three generations of Vietnamese students, including Ngo Minh Khoa, who is currently a PhD student, and Le Cong Truc, who has graduated and is now a postdoctoral researcher in Switzerland.

Nature is a multidisciplinary science journal that has published pioneering research since 1869. It is among the most prestigious publications, and having an article accepted is an honor in any researcher's career. Submissions must meet criteria for novelty, significant scientific impact, and robust methodology, while also attracting interest from the multidisciplinary scientific community.

Khanh Linh