Recruitment of mRNAs to P granules by condensation with intrinsically-disordered proteins

Elife. 2020 Jan 24;9:e52896. doi: 10.7554/eLife.52896.

Abstract

RNA granules are protein/RNA condensates. How specific mRNAs are recruited to cytoplasmic RNA granules is not known. Here, we characterize the transcriptome and assembly of P granules, RNA granules in the C. elegans germ plasm. We find that P granules recruit mRNAs by condensation with the disordered protein MEG-3. MEG-3 traps mRNAs into non-dynamic condensates in vitro and binds to ~500 mRNAs in vivo in a sequence-independent manner that favors embryonic mRNAs with low ribosome coverage. Translational stress causes additional mRNAs to localize to P granules and translational activation correlates with P granule exit for two mRNAs coding for germ cell fate regulators. Localization to P granules is not required for translational repression but is required to enrich mRNAs in the germ lineage for robust germline development. Our observations reveal similarities between P granules and stress granules and identify intrinsically-disordered proteins as drivers of RNA condensation during P granule assembly.

Keywords: C. elegans; MEG-3; RNA granules; cell biology; developmental biology; germ granules; germ line; intrinsically-disordered proteins; phase transition.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / metabolism*
  • Cytoplasmic Granules / metabolism*
  • Germ Cells
  • Immunoprecipitation
  • Intrinsically Disordered Proteins / metabolism*
  • Protein Binding
  • Protein Biosynthesis
  • RNA, Messenger / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • Intrinsically Disordered Proteins
  • RNA, Messenger

Associated data

  • GEO/GSE139878
  • GEO/GSE139880
  • GEO/GSE139879
  • GEO/GSE100652