Spatiotemporal regulation of liquid-like condensates in epigenetic inheritance

Nature. 2018 May;557(7707):679-683. doi: 10.1038/s41586-018-0132-0. Epub 2018 May 16.

Abstract

Non-membrane-bound organelles such as nucleoli, processing bodies, Cajal bodies and germ granules form by the spontaneous self-assembly of specific proteins and RNAs. How these biomolecular condensates form and interact is poorly understood. Here we identify two proteins, ZNFX-1 and WAGO-4, that localize to Caenorhabditis elegans germ granules (P granules) in early germline blastomeres. Later in germline development, ZNFX-1 and WAGO-4 separate from P granules to define an independent liquid-like condensate that we term the Z granule. In adult germ cells, Z granules assemble into ordered tri-condensate assemblages with P granules and Mutator foci, which we term PZM granules. Finally, we show that one biological function of ZNFX-1 and WAGO-4 is to interact with silencing RNAs in the C. elegans germline to direct transgenerational epigenetic inheritance. We speculate that the temporal and spatial ordering of liquid droplet organelles may help cells to organize and coordinate the complex RNA processing pathways that underlie gene-regulatory systems, such as RNA-directed transgenerational epigenetic inheritance.

Publication types

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

MeSH terms

  • Animals
  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism*
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Conserved Sequence
  • DNA-Binding Proteins / metabolism
  • Epigenesis, Genetic / genetics*
  • Germ Cells / metabolism
  • Organelles / chemistry*
  • Organelles / metabolism*
  • RNA Helicases / genetics
  • RNA Helicases / metabolism*
  • RNA Interference*

Substances

  • Argonaute Proteins
  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • WAGO-4 protein, C elegans
  • RNA Helicases
  • ZNFX-1 protein, C elegans