Glucose stress causes mRNA retention in nuclear Nab2 condensates

Cell Rep. 2024 Jan 23;43(1):113593. doi: 10.1016/j.celrep.2023.113593. Epub 2023 Dec 18.

Abstract

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.

Keywords: CP: Cell biology; DEAD-box ATPase Dbp5; Nab2; RNA; condensation; glucose stress; mRNA export.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus
  • Cell Nucleus / metabolism
  • DEAD-box RNA Helicases / metabolism
  • Nuclear Pore Complex Proteins* / metabolism
  • Nucleocytoplasmic Transport Proteins / genetics
  • Nucleocytoplasmic Transport Proteins / metabolism
  • RNA / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins* / metabolism

Substances

  • DEAD-box RNA Helicases
  • Nuclear Pore Complex Proteins
  • Nucleocytoplasmic Transport Proteins
  • RNA
  • RNA, Messenger
  • RNA-Binding Proteins
  • Saccharomyces cerevisiae Proteins
  • NAB2 protein, S cerevisiae