Visualizing splicing dynamics in human cells by cryo-ET

The spliceosome is a dynamic, multicomponent macromolecular complex essential for the precise removal of introns from pre-mRNA. While extensive genetical, biochemical, and structural studies have provided insights into the splicing cycle, the structural dynamics and distribution of spliceosomes within human cells remain only partially understood. In this project, I aim to study the in situ structures of the spliceosome by cryo-electron tomography (cryo-ET) and sub-tomogram averaging, alongside other advanced techniques, to elucidate the dynamic assembly and spatiotemporal distribution of spliceosome, as well as its crosstalks with other nuclear machinery. This research aims to visualize macromolecular complexes in their native environments at near-atomic resolution in the nucleus, providing new insights into the mechanisms of pre-mRNA splicing in human cells.