Condensation of a nuclear mRNA export factor regulates mRNA transport during stress

Abstract

SummaryUnidirectional mRNA transport from the nucleus to the cytoplasm 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 critical process and its regulation is lacking. Here, we use single RNA imaging to show that cells use selective mRNA retention to re-wire mRNA export during stress. We demonstrate that upon glucose withdrawal the essential export factor Nab2 forms RNA-dependent condensates in the nucleus blocking bulk mRNA export while selectively allowing the transport of stress-induced mRNAs. This is accompanied by reduced abundance of the DEAD-box ATPase Dbp5 at the nuclear pore, and experimental Dbp5 depletion triggers Nab2 condensation and nuclear mRNA accumulation. Condensation can be recapitulated in vitro, with Nab2 forming RNA-dependent liquid droplets, which fail to form in the presence of active Dbp5. Our results suggest that cells use condensation to selectively regulate mRNA export and to control gene expression during stress.HighlightsThe nuclear Poly(A)-binding protein Nab2 forms condensates upon acute cellular depletion of the DEAD-box ATPase Dbp5Nab2 dimerization but not its intrinsically disordered regions (IDRs) are essential for condensation in vitro and in vivoGlucose stress leads to global mRNA retention in the nucleus and depends on Nab2 condensationNab2 condensation confers selectivity of RNA retention during glucose stressProper Nab2 condensation is essential for survival after prolonged stress