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In vivo reconstitution finds multivalent RNA-RNA interactions as drivers of mesh-like condensates

  1. Weirui Ma  Is a corresponding author
  2. Gang Zheng
  3. Wei Xie
  4. Christine Mayr  Is a corresponding author
  1. Memorial Sloan Kettering Cancer Center, United States
Research Article
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Cite this article as: eLife 2021;10:e64252 doi: 10.7554/eLife.64252

Abstract

Liquid-like condensates have been thought to be sphere-like. Recently, various condensates with filamentous morphology have been observed in cells. One such condensate is the TIS granule network that shares a large surface area with the rough endoplasmic reticulum and is important for membrane protein trafficking. It has been unclear how condensates with mesh-like shapes, but dynamic protein components are formed. In vitro and in vivo reconstitution experiments revealed that the minimal components are a multivalent RNA-binding protein that concentrates RNAs that are able to form extensive intermolecular mRNA-mRNA interactions. mRNAs with large unstructured regions have a high propensity to form a pervasive intermolecular interaction network that acts as condensate skeleton. The underlying RNA matrix prevents full fusion of spherical liquid-like condensates, thus driving the formation of irregularly shaped membraneless organelles. The resulting large surface area may promote interactions at the condensate surface and at the interface with other organelles.

Data availability

All raw data are included as supplementary Excel files in the manuscript.

The following previously published data sets were used

Article and author information

Author details

  1. Weirui Ma

    Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, United States
    For correspondence
    maweirui@zju.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  2. Gang Zheng

    Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Wei Xie

    Structural Biology, Memorial Sloan Kettering Cancer Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Christine Mayr

    Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, United States
    For correspondence
    mayrc@mskcc.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7084-7608

Funding

NIH Office of the Director (DP1-GM123454)

  • Christine Mayr

National Cancer Institute (P30 CA008748)

  • Christine Mayr

Pershing Square Sohn Cancer Research Alliance

  • Christine Mayr

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 22, 2020
  2. Accepted: March 1, 2021
  3. Accepted Manuscript published: March 2, 2021 (version 1)
  4. Version of Record published: March 17, 2021 (version 2)

Copyright

© 2021, Ma 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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