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Spatiotemporal regulation of liquid-like condensates in epigenetic inheritance

Author

Listed:
  • Gang Wan

    (Harvard Medical School)

  • Brandon D. Fields

    (Harvard Medical School
    University of Wisconsin-Madison)

  • George Spracklin

    (Harvard Medical School
    University of Wisconsin-Madison)

  • Aditi Shukla

    (Harvard Medical School)

  • Carolyn M. Phillips

    (University of Southern California)

  • Scott Kennedy

    (Harvard Medical School)

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.

Suggested Citation

  • Gang Wan & Brandon D. Fields & George Spracklin & Aditi Shukla & Carolyn M. Phillips & Scott Kennedy, 2018. "Spatiotemporal regulation of liquid-like condensates in epigenetic inheritance," Nature, Nature, vol. 557(7707), pages 679-683, May.
    • Handle: RePEc:nat:nature:v:557:y:2018:i:7707:d:10.1038_s41586-018-0132-0
    DOI: 10.1038/s41586-018-0132-0
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    Cited by:

    1. Emily L. Spaulding & Alexis M. Feidler & Lio A. Cook & Dustin L. Updike, 2022. "RG/RGG repeats in the C. elegans homologs of Nucleolin and GAR1 contribute to sub-nucleolar phase separation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Wenjun Chen & Jordan S. Brown & Tao He & Wei-Sheng Wu & Shikui Tu & Zhiping Weng & Donglei Zhang & Heng-Chi Lee, 2022. "GLH/VASA helicases promote germ granule formation to ensure the fidelity of piRNA-mediated transcriptome surveillance," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Ian F. Price & Jillian A. Wagner & Benjamin Pastore & Hannah L. Hertz & Wen Tang, 2023. "C. elegans germ granules sculpt both germline and somatic RNAome," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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