Protein-based condensation mechanisms drive the assembly of RNA-rich P granules

Elife. 2021 Jun 9:10:e63698. doi: 10.7554/eLife.63698.


Germ granules are protein-RNA condensates that segregate with the embryonic germline. In Caenorhabditis elegans embryos, germ (P) granule assembly requires MEG-3, an intrinsically disordered protein that forms RNA-rich condensates on the surface of PGL condensates at the core of P granules. MEG-3 is related to the GCNA family and contains an N-terminal disordered region (IDR) and a predicted ordered C-terminus featuring an HMG-like motif (HMGL). We find that MEG-3 is a modular protein that uses its IDR to bind RNA and its C-terminus to drive condensation. The HMGL motif mediates binding to PGL-3 and is required for co-assembly of MEG-3 and PGL-3 condensates in vivo. Mutations in HMGL cause MEG-3 and PGL-3 to form separate condensates that no longer co-segregate to the germline or recruit RNA. Our findings highlight the importance of protein-based condensation mechanisms and condensate-condensate interactions in the assembly of RNA-rich germ granules.

Keywords: C. elegans; P granule; RNA granule; cell biology; developmental biology; germ plasm; intrinsically disordered protein; phase separation.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / metabolism*
  • Cytoplasmic Granules / chemistry
  • Cytoplasmic Granules / metabolism*
  • Embryo, Nonmammalian
  • Intrinsically Disordered Proteins / chemistry
  • Intrinsically Disordered Proteins / metabolism*
  • RNA, Helminth / chemistry
  • RNA, Helminth / metabolism*


  • Caenorhabditis elegans Proteins
  • Intrinsically Disordered Proteins
  • MEG-3 protein, C elegans
  • RNA, Helminth