Recently, Shi Yigong's team published an eye-catching article in the journal Nature Structure and Molecular Biology, entitled "Structural insights of human spliceosomes corrected by branching sites".
This study reveals the high-resolution structure of the human 17S U2 SNRNP complex and the spliceosome Pre-A complex, providing important molecular mechanistic information for understanding how the spliceosome selects and corrects branching sites.
The results of this research are of far-reaching significanceNot only does it help unravel the early assembly process of the spliceosome, but it also provides key insights into the sf3b1 mutation associated with cancer.
Spliceosomes: the key to gene expressionSplices are important molecular machines in the gene expression process, responsible for properly splicing coding exons with non-coding introns in gene information to generate mature RNA molecules. This process is essential for normal gene expression as it determines the nature and function of the proteins produced.
However, the work of the spliceosome is not all smooth sailing. It requires the selection of the correct branching site, while also being corrected to ensure that there are no false splicing events. In the past, scientists have been exploring how spliceosomes carry out these critical operations at the molecular level.
Unraveling the mysteries of molecular mechanismsThe latest research by Shi Yigong's team provides valuable structural information to help us better understand how spliceosomes work. Through high-resolution structural analysis, the researchers found that during the early assembly of the spliceosome, PRP5 binds to the 17S U2 SNRNP and occupies the RNA channel of SF3B1 through its acidic loop. In addition, the helicase domain of PRP5 binds to the U2 snRNA, while the BS-interacting stem loop of the U2 snRNA is shielded by Tat-SF1, preventing it from binding to the BS (branching site).
In the Pre-A complex, the researchers observed the initial U2-BS duplex formation, while the translocation helicase domain of PRP5 remained consistent with the U2 snRNA, continuing to occupy the RNA channel. At this time, the Pre-A complex is specifically stabilized by the splicing factors SF1, DNAJC8, and SF3A2.
Breakthrough discoveryThe team's work also revealed that cancer-derived mutations in SF3B1 are associated with the RNA helicase prp5. This finding provides key insights into our understanding of the pathogenic mechanisms of cancer-associated SF3B1 mutations. This means that this study will not only help solve the puzzle of spliceosome work, but may also provide new ideas for cancer research and **.
Shi Yigong's research team has been exploring cutting-edge science and has continuously achieved breakthrough results. Their work not only contributes to the development of the basic life sciences, but also makes outstanding contributions to the improvement of China's scientific and technological capabilities.
Shi Yigong himself is also an outstanding representative in the field of scientific research and education. He not only works diligently in the laboratory to solve scientific problems, but also devotes himself to cultivating young scientific talents. He firmly believes that talent is the core competitiveness of national development, so he has been working hard to train scientists and promote the reform of the scientific research system.
To do scientific research, we must dare to face difficulties
In 2015, they were the first to resolve the spatial three-dimensional structure of RNA spliceosomes, which is a huge challenge because the elucidation of the atomic structure of spliceosomes has always been a difficult problem to overcome. This achievement has been hailed as a milestone breakthrough in the field of RNA splicing, and has also been included on the cover of the international classic textbook "Principles of Biochemistry".
Behind the groundbreaking scientific research work is countless days and nights of hard work. Shi Yigong and his team are not afraid of difficulties, purchasing experimental equipment, mastering cutting-edge technology, conducting data collection and complex structural analysis, all of which require great patience and perseverance. In the most difficult moments, they worked 16 hours a day, and Shi Yigong was always the last person to leave the laboratory.
However, the satisfaction of scientific breakthroughs is short-lived, replaced by constant stress and restlessness. However, it is this relentless pursuit and love of science that pushes them to continue to climb the heights of science.
The achievements of Shi Yigong's team in the field of RNA spliceosomes do not stop there. Over the next few years, they made a series of world-class breakthroughs. In 2017, they unraveled the structure of the first human spliceosome for the first time, providing key information for a deeper understanding of how spliceosomes work. In 2021, they resolved the high-resolution 3D structure of minor spliceosomes for the first time, opening up a new direction for research in this field.
In addition, they have also made important progress in studying the important protein structure secretase of Alzheimer's disease. This series of breakthroughs has forged their scientific reputation and made them shining stars in the international research field.
Shi Yigong is not only satisfied with his achievements, he has set his scientific research sights on a more cutting-edge field - quantum biology. He firmly believes that if China's basic research and core technologies cannot be truly strong, it will be a major problem for a generation of scientific research workers. Therefore, he actively pursues innovation and bravely climbs the pinnacle of science.
Cultivating talents for the countryShi Yigong is well aware that the core competitiveness of China's future development is talent. Therefore, in 2018, he made the bold decision to leave Tsinghua University, rise to the position of vice president, and found a new type of research university, Westlake University. He firmly believes that to build the world's innovation highland, it is necessary to have world-class top talents.
His requirements for young doctoral supervisors are also quite innovative, not only do they not evaluate the publication of articles, patents, titles and awards, but the only requirement is to make original and indispensable scientific contributions in their field after 6 years. This unique training model aims to inspire young scientific talents to reach new heights of science.
Shi Yigong is not only an outstanding scientific researcher, but also an outstanding educator. He taught his knowledge, ideas and scientific thinking, influencing a large number of young people. He likes nothing more than being called "teacher" by his students and keeping in touch with young people and caring about their growth and development.
In the journey of science, we look forward to more determined dreamers like Shi Yigong to work hard for the progress of science and the future of mankind.