Nuclear pore complex and ribosome assembly
1.Structure and assembly 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.
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. 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. Another complex, which contains transcription and export factors (termed TREX-2) also functions in transcription-coupled mRNA export. In this project, we analyze how the nuclear pore-associated TREX-2 mRNA export complex is assembled and bound to the NPC (in collaboration with Murray Stewart, MRC Cambridge, England). Tethering of genes to the nuclear periphery could ultimately bring nascent transcripts into the vicinity of the nuclear pore-associated mRNA export machinery.
Download BZH Report Hurt 2014-2016
• Ueli Aebi, University of Basel, CH
• Olivier Gadal, Institut Pasteur Paris, F
• Johannes Lechner, University of Heidelberg (BZH), D
• Robin Reed, Harvard Medical School Boston, USA
• Georgios Simos, University of Thessaly, GR
• Irmi Sinning, University of Heidelberg (BZH), D
• David Tollervey, University of Edinburgh, UK
• Herbert Tschochner, University of Regensburg, D
Research grant (DFG) on formation, maturation and nuclear export of pre-ribosomal subunits;
Research grant (DFG) on reconstitution of the nuclear pore complex;
Advanced Grant (ERC) "GLOWSOME" on eucaryotic ribosome assembly.