RNA promotes phase separation of glycolysis enzymes into yeast G bodies in hypoxia

Elife. 2020 Apr 16;9:e48480. doi: 10.7554/eLife.48480.

Abstract

In hypoxic stress conditions, glycolysis enzymes assemble into singular cytoplasmic granules called glycolytic (G) bodies. G body formation in yeast correlates with increased glucose consumption and cell survival. However, the physical properties and organizing principles that define G body formation are unclear. We demonstrate that glycolysis enzymes are non-canonical RNA binding proteins, sharing many common mRNA substrates that are also integral constituents of G bodies. Targeting nonspecific endoribonucleases to G bodies reveals that RNA nucleates G body formation and maintains its structural integrity. Consistent with a phase separation mechanism of biogenesis, recruitment of glycolysis enzymes to G bodies relies on multivalent homotypic and heterotypic interactions. Furthermore, G bodies fuse in vivo and are largely insensitive to 1,6-hexanediol, consistent with a hydrogel-like composition. Taken together, our results elucidate the biophysical nature of G bodies and demonstrate that RNA nucleates phase separation of the glycolysis machinery in response to hypoxic stress.

Keywords: RNA; S. cerevisiae; cell biology; glycolysis; hypoxia; phase separation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cytoplasmic Granules / metabolism*
  • Endoribonucleases / metabolism
  • Glycolysis / physiology*
  • RNA, Fungal / metabolism*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • RNA, Fungal
  • Saccharomyces cerevisiae Proteins
  • Endoribonucleases

Associated data

  • GEO/GSE65992
  • GEO/GSE145881
  • GEO/GSE43747