The role of nuclear pores in regulating gene expression

Nuclear pore complexes (NPCs) are large macromolecular assemblies in the nuclear envelope, which regulate the transport of molecules between the nucleus and cytoplasm. The recent years have shown that NPCs are not merely transport channels but influence a broad range of nuclear activities. Gene expression in eukaryotes requires several multi-component cellular machines. Each machine carries out a separate step in the gene expression pathway, which includes transcription, RNA processing and the export of mature mRNA to the cytoplasm. Nuclear pores play an important role in coordinating these steps by anchoring activated genes. Indeed, certain genes move from the nuclear interior to the nuclear periphery, where they interact with NPCs. This anchoring step requires specialized adaptor proteins. We study these adaptors to unravel how the NPCs physically connect to the genome to regulate its architecture and function.

The cell nucleus is like a fortified city, in which lipid membranes form a defensive wall, and nuclear pore complexes (NPCs) function as gates that control the transport of cargo across these walls. Notably, these city gates not only provide a point of controlled entry and departure, but are zones of molecular communication and trade. In this project we have identified a molecular mechanism by which nuclear pores communicate with the gene expression machinery to regulate the decoding of the eukaryotic genome. We have further revealed how the modification of chromatin with ubiquitin is established to impact on transcription. Finally, we could assign a new function to the nuclear pore basket by demonstrating its ability to regulate the shape of the nuclear envelope membrane and assembly of NPCs. Together these findings advance our understanding of key aspects of nuclear cell biology, which is relevant for health and disease.