Recently, the research team led by Wan Bingbing from Shanghai Jiao Tong University's Institute of Systems Biomedicine, in collaboration with the Ming Lei and Jian Wu’s team from the Institute of Precision Medicine, published an online article in the Cell sister journal Structure titled "Structural and functional insights into CST tethering in Tetrahymena thermophila telomerase." This article revealed the molecular mechanism of how the CST telomere protection protein complex is connected to the catalytic core of telomerase in Tetrahymena thermophila, providing a foundation for further research and elucidation of the CST complex-mediated telomere synthesis mechanism.

In this study, structural biology techniques such as NMR were first used as the research method to identify important amino acids that affect the interaction between p50 and the CST complex. The significance of these amino acids was then verified through yeast two-hybrid and in vivo co-IP methods.

Subsequently, they found that the mutation of the key amino acid phenylalanine F233 of the p50 protein had a significant impact on the length of both the G and C strands of Tetrahymena thermophila telomeres, as detected by length analysis. In particular, the mutation severely shortened the length of the C strand. These structural findings suggest that the p50 protein's F233 site, which interacts through hydrophobic interactions, plays an important role in regulating telomere length.

This study used the model organism Tetrahymena. thermophila as a research model, and its findings have expanded our understanding of the fundamental scientific question of telomere synthesis mechanisms.

Dr. Wan Bingbing, the principle investigator from the Genomic Instability and Tumorigenesis Research Group at the Institute of Systems Biomedicine, Shanghai Jiao Tong University, and Professors Lei Ming and Wu Jian from the Institute of Precision Medicine at Shanghai Jiao Tong University School of Medicine, are the corresponding authors of this paper. Dr. Ma Yuanyuan, a postdoctoral fellow at the Institute of Precision Medicine, is the first author, and Cao Yu, a doctoral student from the Institute of Systems Biomedicine, is a co-author. This study was supported by grants from the National Natural Science Foundation of China, the Shanghai Municipal Science and Technology Commission, and National Facility for Translational Medicine (Shanghai), China.

Original article link: https://www.sciencedirect.com/science/article/pii/S0969212622003938