Glucose stress causes mRNA retention in nuclear Nab2 condensates
Stephanie Heinrich,
Maria Hondele,
Désirée Marchand,
Carina Patrizia Derrer,
Mostafa Zedan,
Alexandra Oswald,
Liliana Malinovska,
Federico Uliana,
Sarah Khawaja,
Roberta Mancini,
David Grunwald,
Karsten Weis
Affiliations
Stephanie Heinrich
Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), 8093 Zurich, Switzerland; Corresponding author
Maria Hondele
Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), 8093 Zurich, Switzerland; Biozentrum, Center for Molecular Life Sciences, University of Basel, 4056 Basel, Switzerland
Désirée Marchand
Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), 8093 Zurich, Switzerland
Carina Patrizia Derrer
Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), 8093 Zurich, Switzerland
Mostafa Zedan
Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), 8093 Zurich, Switzerland
Alexandra Oswald
Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), 8093 Zurich, Switzerland
Liliana Malinovska
Department of Biology, Institute of Molecular Systems Biology, Swiss Federal Institute of Technology (ETH), 8093 Zurich, Switzerland
Federico Uliana
Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), 8093 Zurich, Switzerland
Sarah Khawaja
Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), 8093 Zurich, Switzerland
Roberta Mancini
Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), 8093 Zurich, Switzerland
David Grunwald
University of Massachusetts Chan Medical School, RNA Therapeutics Institute, Worcester, MA 01605, USA
Karsten Weis
Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), 8093 Zurich, Switzerland; Corresponding author
Summary: Nuclear mRNA export via nuclear pore complexes is an essential step in eukaryotic gene expression. Although factors involved in mRNA transport have been characterized, a comprehensive mechanistic understanding of this process and its regulation is lacking. Here, we use single-RNA imaging in yeast to show that cells use mRNA retention to control mRNA export during stress. We demonstrate that, upon glucose withdrawal, the essential RNA-binding factor Nab2 forms RNA-dependent condensate-like structures in the nucleus. This coincides with a reduced abundance of the DEAD-box ATPase Dbp5 at the nuclear pore. Depleting Dbp5, and consequently blocking mRNA export, is necessary and sufficient to trigger Nab2 condensation. The state of Nab2 condensation influences the extent of nuclear mRNA accumulation and can be recapitulated in vitro, where Nab2 forms RNA-dependent liquid droplets. We hypothesize that cells use condensation to regulate mRNA export and control gene expression during stress.
