Department of Molecular & Cell Biology
University of California, Berkeley
C142 Life Sciences Addition #3200
Berkeley, CA 94720-3200
2000 Searle Scholar
Our laboratory studies macromolecular transport into and out of the nucleus in eukaryotic cells. The high degree of compartmentalization in eukaryotes causes a spatial separation of cellular processes such as DNA transcription and mRNA translation. This leads to the bi-directional exchange of a large number of macromolecules between the nuclear and cytoplasmic compartments and allows additional levels of control in eukaryotic gene expression. The site of exchange is the nuclear pore complex (NPC), a multiprotein structure, consisting of probably more than 100 different polypeptides. Every minute several thousand macromolecules are transported through a single NPC in both directions. Export cargoes include different classes of RNA such as messenger RNA (mRNA) , ribosomal RNA (rRNA), transfer RNA (tRNA), and small nuclear RNAs (snRNAs). In the opposite direction, a large number of proteins and matured snRNP particles are actively imported into the nucleoplasm. In addition, a number of proteins have been shown to shuttle between the nucleus and the cytoplasm. Despite recent progress in our understanding of nucleocytoplasmic transport processes many fundamental questions remain. For example, the export of mRNA from the nucleus into the cytoplasm, a key step in the control of eukaryotic gene expression, is still very poorly understood. Also, the actual mechanism how macromolecules are translocated through the NPC is largely unknown. We combine genetic and biochemical approaches in S. cerevisiae and metazoan cells to characterize the molecular machinery responsible for the transport of macromolecules through the NPC.
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