Modulation of RNA Condensation by the DEAD-Box Protein eIF4A

Cell. 2020 Feb 6;180(3):411-426.e16. doi: 10.1016/j.cell.2019.12.031. Epub 2020 Jan 9.

Abstract

Stress granules are condensates of non-translating mRNAs and proteins involved in the stress response and neurodegenerative diseases. Stress granules form in part through intermolecular RNA-RNA interactions, and to better understand how RNA-based condensation occurs, we demonstrate that RNA is effectively recruited to the surfaces of RNA or RNP condensates in vitro. We demonstrate that, through ATP-dependent RNA binding, the DEAD-box protein eIF4A reduces RNA condensation in vitro and limits stress granule formation in cells. This defines a function for eIF4A to limit intermolecular RNA-RNA interactions in cells. These results establish an important role for eIF4A, and potentially other DEAD-box proteins, as ATP-dependent RNA chaperones that limit the condensation of RNA, analogous to the function of proteins like HSP70 in combatting protein aggregates.

Keywords: DEAD-box protein; RNA chaperone; RNA-RNA interaction; biomolecular condensate; ribonucleoprotein; stress granule.

Publication types

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

MeSH terms

  • Adenosine Triphosphate / metabolism
  • DEAD-box RNA Helicases / metabolism*
  • Eukaryotic Initiation Factor-4A / metabolism*
  • Eukaryotic Initiation Factor-4F / metabolism*
  • HeLa Cells
  • Humans
  • Microscopy, Confocal
  • Protein Binding
  • RNA Helicases / metabolism*
  • RNA, Fungal / isolation & purification
  • RNA, Fungal / metabolism*
  • RNA, Messenger / metabolism
  • Recombinant Proteins / metabolism
  • Ribonucleoproteins / metabolism*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Time-Lapse Imaging

Substances

  • EIF4A1 protein, human
  • Eukaryotic Initiation Factor-4F
  • RNA, Fungal
  • RNA, Messenger
  • Recombinant Proteins
  • Ribonucleoproteins
  • Saccharomyces cerevisiae Proteins
  • messenger ribonucleoprotein
  • Adenosine Triphosphate
  • Eukaryotic Initiation Factor-4A
  • DEAD-box RNA Helicases
  • RNA Helicases
  • TIF1 protein, S cerevisiae