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.


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.