"The role of DEAD-box ATPases in the regulation of ribonucleoprotein complex condensation"
Karsten Weis is a Professor of Cellular Dynamics at the ETH Zürich. The Weis group has a long-standing interest in understanding how cells are organized and how macromolecules are transported within cells. The initial focus of the team was to understand how molecules are transported across the nuclear pore complex (NPC), the channel that mediates all nucleocytoplasmic transport processes. Over the years, the Weis group has made significant contributions to this field, including the first characterizations of nuclear protein import and export receptors, the demonstration of a RanGTP gradient within cells, the identification of distinct selectivity filters within the NPC, the first structural characterization of the ATPase cycle of the mRNA export factor Dbp5 and the characterization of the NPC assembly pathway. More recently, the Weis group has also studied how RNAs are partitioned and localized to membraneless organelles, which led to the discovery that RNA-containing phase-separated condensates are globally regulated by DEAD-box ATPases. This revealed a unifying principle of how this enzyme family controls the dynamics of membraneless organelles in both pro- and eukaryotic cells. The team’s work on intracellular transport has also led to the surprising finding that cells regulate their diffusional properties when starved for nutrients and enter a state of dormancy.
Key references from the Weis lab:
- Weis, K., Mattaj, I. W. & Lamond, A. I. Identification of hSRP1 alpha as a functional receptor for nuclear localization sequences. Science 268, 1049–1053 (1995).
- Stade, K., Ford, C. S., Guthrie, C. & Weis, K. Exportin 1 (Crm1p) is an essential nuclear export factor. Cell 90, 1041–1050 (1997).
- Kalab, P., Weis, K. & Heald, R. Visualization of a Ran-GTP gradient in interphase and mitotic Xenopus egg extracts. Science 295, 2452–2456 (2002).
- Kalab, P., Pralle, A., Isacoff, E. Y., Heald, R. & Weis, K. Analysis of a RanGTP-regulated gradient in mitotic somatic cells. Nature 440, 697–701 (2006).
- Lowe, A. R. et al. Selectivity mechanism of the nuclear pore complex characterized by single cargo tracking. Nature 467, 600–603 (2010).
- Montpetit, B. et al. A conserved mechanism of DEAD-box ATPase activation by nucleoporins and InsP6 in mRNA export. Nature 472, 238–242 (2011).
- Joyner, R. P. et al. A glucose-starvation response regulates the diffusion of macromolecules. Elife 5, (2016).
- Onischenko, E. et al. Natively Unfolded FG Repeats Stabilize the Structure of the Nuclear Pore Complex. Cell 171, 904–917.e19 (2017).
- Hondele, M. et al. DEAD-box ATPases are global regulators of phase-separated organelles. Nature 573, 144–148 (2019).
- Onischenko, E. et al. Maturation Kinetics of a Multiprotein Complex Revealed by Metabolic Labeling. Cell 183, 1785–1800.e26 (2020).