Structural and mechanistic investigations of the spliceosome

Abstract:Dr. Shi’s group has been focusing on the structural and mechanistic elucidation of pre-mRNA splicing in the past decades. After the success of crystal structural elucidation of subcomplexes within spliceosome, they took a direct assault on the intact spliceosome and made the breakthrough in the summer of 2015. They determined the structure of intron lariat spliceosome ILS complex from S. pombe at an average resolution of 3.6 ?, which is the first atomic structure of the intact spliceosome, revealing the organization of the spliceosomal components and the conformation of the splicing active site for the first time in the world. Since then, Dr. Shi’s group has reported the high-resolution structures of the spliceosome in all eight major fully-assembled functional states, as well as the structure of the largest pre-assembled subcomplex U4/U6.U5 tri-snRNP from S. cerevisiae. The ten structures give rise to a complete structural view for spliceosome activation, catalysis and disassembly. His group also captured 7 key intermediates of human spliceosome, providing structural basis of the evolution of the spliceosome machinery from lower to higher eukaryotes. Taken together, these accomplishments represent a major contribution in this field, which conceptionally advance our understanding to the molecular mechanism of pre-mRNA splicing and provide unprecedented insights into the research on pathogenesis of related diseases and drug discovery.

Awardee:Yigong Shi, was born in Zhengzhou, Henan Province in 1967. He is a structural biologist and university professor in Tsinghua University. Dr. Shi is an Academician of the Chinese Academy of Sciences, a Fellow of the American Association for Advancement of Sciences, an Honorary Foreign Member of the American Academy of Arts and Sciences, a Foreign Associate of the US National Academy of Sciences, and a Foreign Associate of the European Molecular Biology Organization. Shi received his Bachelor's Degree from Tsinghua University in 1989 and Ph.D. in Biophysics at Johns Hopkins University School of Medicine in 1995. He performed his post-doctoral research at the Memorial Sloan-Kettering Cancer Center. He joined Princeton University as an Assistant Professor in 1998 and was promoted to Full Professor in 2003. He was named the Warner-Lambert/Parke-Davis Professor of Molecular Biology at Princeton University in 2007. Dr. Shi declined an offer as an investigator of the Howard Hughes Medical Institute and returned to Tsinghua University in 2008. Dr. Shi is the Founding President of Westlake University, vice chairman of China Association of Science and Technology and the Dean of the Institute of Biomedicine of Tsinghua University.
Dr. Yigong Shi's research has provided important insights into programmed cell death and regulated intramembrane proteolysis. His pioneering research on caspase activation, inhibition, and derepression markedly advanced mechanistic understanding of programmed cell death. He has made fantastic breakthrough in the area of “genetic central dogma” by reporting the first three-dimensional structure of an intact yeast spliceosome. For his research contributions, Dr. Shi received a number of recognitions, including Searle Scholar, Rita Allen Schola. Irving Sigal Young Investigator Award, Sackler Prize, QiuShi Distinguished Scientist Award, Gregori Aminoff Prize, Future Science Prize Life Science Award, Tan Jiazhen Life Science Distinguished Scientist Award, The Ho Leung Ho Lee Distinguished Scientist Award.