High-resolution structural and mechanistic analyses of spliceosomal complexes and other RNPs by cryo-EM (P07)

• Subject Area: Structural Biology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 469281184

Pre-mRNA splicing is a highly dynamic and complex process. Great progress has recently been made in solving structures of the major assembly and functional states of the spliceosome by cryo-EM. However, there are still many limitations and open questions. The dynamic range of the spliceosome is extremely large and therefore we will study more intermediate structural states of the splicing process. Additionally, large parts of the spliceosome are not resolved due to their high mobility. Finally, the resolution needs to be improved to better understand the mechanistic and regulatory aspects of splicing. We will use small molecule splicing inhibitors to visualize more details of the conformational landscape of the spliceosome and employ our recently installed and updated unique cryo-EM that is especially suited to significantly improve the resolution of spliceosome structures.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1565: Molecular mechanisms and interplay of gene expression processes
• Applicant Institution: Georg-August-Universität Göttingen
• Project Head: Professor Dr. Holger Stark