Nuclear Pores and Nucleocytoplasmic Transport
Groupleader: Ed Hurt
Gene Expression and Nuclear Export from the Nucleus
1. Connections between transcription and mRNA export
Gene expression requires bi-directional transport of macromolecules across the nuclear membrane. Among the many components that are exported from the nucleus are messenger RNAs, which are transcribed as pre-mRNAs in the nucleus, followed by RNA processing and modification, RNP assembly and nuclear export. Our studies revealed that the TREX complex, which contains components involved in transcription elongation (THO complex members) and mRNA export (Sub2, Yra1), acts as a coupling device in transcription-coupled mRNA export. We are studying how the TREX members are co-transcriptionally recruited to active genes during transcription elongation and how the TREX complex couples transcription elongation with mRNP assembly and nuclear export.
Another complex, which contains transcription and export factors (termed TREX-2) also functions in transcription-coupled mRNA export. In this project, we analyze whether actively transcribed genes become tethered to the nuclear pores via Sus1, which is both a subunit of the SAGA transcription complex (which binds to chromatin) and the nuclear pore-associated TREX-2 mRNA export complex (in collaboration with the Nehrbass lab, Institute Pasteur, Paris, France). Tethering of genes to the nuclear periphery could ultimately bring nascent transcripts into the vicinity of the nuclear pore-associated mRNA export machinery.
2. Formation and nuclear export of ribosomes
Ribosome formation is a complicated and highly regulated multistep process, which requires more than 150 conserved, mostly essential non-ribosomal factors (e.g. helicases, rRNA processing factors, ATPases, GTPases, Kinases, export factors), which transiently associate with the evolving pre-ribosomal particles. Our studies focus on late steps of ribosome formation and the coupling to nuclear export.
3. Formation of the nuclear pore complex
Nuclear pore complexes are huge transport machines that span the double nuclear membrane and mediate nucleocytoplasmic traffic. About 60 MDa in size (in yeast), each NPC consists of 30 subunits (nucleoporins), which assemble into an eight-fold symmetrical complex with distinct substructures. To date, little is known about how this huge complex assembles, and which nucleoporins constitute the distinct substructures. We have chosen a reconstitution approach to study the structure-function relationships of the NPC in detail. A detailed structural analysis of the reconstituted NPC will be crucial to understand how nucleocytoplasmic transport through the nuclear pore complex occurs at the atomic level.
Download BZH Report Hurt 2008-2010