Spatiotemporal regulation of liquid-like condensates in epigenetic inheritance

Gang Wan, Brandon D. Fields, George Spracklin, Aditi Shukla, Carolyn M. Phillips and Scott Kennedy ()
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Gang Wan: Harvard Medical School
Brandon D. Fields: Harvard Medical School
George Spracklin: Harvard Medical School
Aditi Shukla: Harvard Medical School
Carolyn M. Phillips: University of Southern California
Scott Kennedy: Harvard Medical School

Nature, 2018, vol. 557, issue 7707, 679-683

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41586-018-0132-0

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