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

  1. Helen Schmidt
  2. Andrea Putnam
  3. Dominique Rasoloson
  4. Geraldine Seydoux  Is a corresponding author
  1. Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, United States
  2. Johns Hopkins University School of Medicine, United States
Research Article
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Cite this article as: eLife 2021;10:e63698 doi: 10.7554/eLife.63698

Abstract

Germ granules are protein-RNA condensates that segregate with the embryonic germline. In C. 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 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.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2-5.

Article and author information

Author details

  1. Helen Schmidt

    Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3449-2790
  2. Andrea Putnam

    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7985-142X
  3. Dominique Rasoloson

    Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2210-1569
  4. Geraldine Seydoux

    Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States
    For correspondence
    gseydoux@jhmi.edu
    Competing interests
    Geraldine Seydoux, serves on the Scientific Advisory Board of Dewpoint Therapeutics, Inc..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8257-0493

Funding

National Institutes of Health (5R37HD037047)

  • Helen Schmidt
  • Andrea Putnam
  • Dominique Rasoloson
  • Geraldine Seydoux

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Robert H Singer, Albert Einstein College of Medicine, United States

Publication history

  1. Received: October 2, 2020
  2. Accepted: June 8, 2021
  3. Accepted Manuscript published: June 9, 2021 (version 1)
  4. Accepted Manuscript updated: June 14, 2021 (version 2)

Copyright

© 2021, Schmidt et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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