Micellar TIA1 with folded RNA binding domains as a model for reversible stress granule formation

Proc Natl Acad Sci U S A. 2020 Dec 15;117(50):31832-31837. doi: 10.1073/pnas.2007423117. Epub 2020 Nov 30.


TIA1, a protein critical for eukaryotic stress response and stress granule formation, is structurally characterized in full-length form. TIA1 contains three RNA recognition motifs (RRMs) and a C-terminal low-complexity domain, sometimes referred to as a "prion-related domain" or associated with amyloid formation. Under mild conditions, full-length (fl) mouse TIA1 spontaneously oligomerizes to form a metastable colloid-like suspension. RRM2 and RRM3, known to be critical for function, are folded similarly in excised domains and this oligomeric form of apo fl TIA1, based on NMR chemical shifts. By contrast, the termini were not detected by NMR and are unlikely to be amyloid-like. We were able to assign the NMR shifts with the aid of previously assigned solution-state shifts for the RRM2,3 isolated domains and homology modeling. We present a micellar model of fl TIA1 wherein RRM2 and RRM3 are colocalized, ordered, hydrated, and available for nucleotide binding. At the same time, the termini are disordered and phase separated, reminiscent of stress granule substructure or nanoscale liquid droplets.

Keywords: RNA binding protein; membranelles organelles; prion; solid-state NMR; 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

  • Intrinsically Disordered Proteins / metabolism
  • Intrinsically Disordered Proteins / ultrastructure*
  • Magnetic Resonance Spectroscopy
  • Micelles
  • Microscopy, Electron
  • Models, Molecular
  • Protein Folding
  • Protein Multimerization
  • RNA-Binding Motifs
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / ultrastructure
  • T-Cell Intracellular Antigen-1 / metabolism
  • T-Cell Intracellular Antigen-1 / ultrastructure*


  • Intrinsically Disordered Proteins
  • Micelles
  • Recombinant Proteins
  • T-Cell Intracellular Antigen-1
  • Tia1 protein, mouse