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Title: Spontaneous driving forces give rise to protein-RNA condensates with coexisting phases and complex material properties

Abstract

Phase separation of multivalent protein and RNA molecules underlies the biogenesis of biomolecular condensates such as membraneless organelles. In vivo, these condensates encompass hundreds of distinct types of molecules that typically organize into multilayered structures supporting the differential partitioning of molecules into distinct regions with distinct material properties. The interplay between driven (active) versus spontaneous (passive) processes that are required for enabling the formation of condensates with coexisting layers of distinct material properties remains unclear. Here, we deploy systematic experiments and simulations based on coarse-grained models to show that the collective interactions among the simplest, biologically relevant proteins and archetypal RNA molecules are sufficient for driving the spontaneous emergence of multilayered condensates with distinct material properties. These studies yield a set of rules regarding homotypic and heterotypic interactions that are likely to be relevant for understanding the interplay between active and passive processes that control the formation of functional biomolecular condensates.

Authors:
 [1]; ORCiD logo [2];  [3];  [4];  [4];  [3];  [5]; ORCiD logo [6];  [7]; ORCiD logo [2];  [1]
  1. Stanford Univ. School of Medicine, CA (United States)
  2. Washington Univ., St. Louis, MO (United States)
  3. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Univ. of California, San Francisco, CA (United States)
  4. Vrije Universiteit Brussel, Brussels (Belgium)
  5. Vlaams Instituut voor Biotechnologie, Leuven (Belgium); KU Leuven (Belgium)
  6. Stanford Univ., CA (United States)
  7. Vrije Universiteit Brussel, Brussels (Belgium); Hungarian Academy of Sciences, Budapest (Hungary)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
OSTI Identifier:
1559207
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 116; Journal Issue: 16; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; phase transitions; biomolecular condensates; complex coacervation; RNA; intrinsically disordered proteins

Citation Formats

Boeynaems, Steven, Holehouse, Alex S., Weinhardt, Venera, Kovacs, Denes, Van Lindt, Joris, Larabell, Carolyn, Van Den Bosch, Ludo, Das, Rhiju, Tompa, Peter S., Pappu, Rohit V., and Gitler, Aaron D. Spontaneous driving forces give rise to protein-RNA condensates with coexisting phases and complex material properties. United States: N. p., 2019. Web. doi:10.1073/pnas.1821038116.
Boeynaems, Steven, Holehouse, Alex S., Weinhardt, Venera, Kovacs, Denes, Van Lindt, Joris, Larabell, Carolyn, Van Den Bosch, Ludo, Das, Rhiju, Tompa, Peter S., Pappu, Rohit V., & Gitler, Aaron D. Spontaneous driving forces give rise to protein-RNA condensates with coexisting phases and complex material properties. United States. doi:10.1073/pnas.1821038116.
Boeynaems, Steven, Holehouse, Alex S., Weinhardt, Venera, Kovacs, Denes, Van Lindt, Joris, Larabell, Carolyn, Van Den Bosch, Ludo, Das, Rhiju, Tompa, Peter S., Pappu, Rohit V., and Gitler, Aaron D. Fri . "Spontaneous driving forces give rise to protein-RNA condensates with coexisting phases and complex material properties". United States. doi:10.1073/pnas.1821038116. https://www.osti.gov/servlets/purl/1559207.
@article{osti_1559207,
title = {Spontaneous driving forces give rise to protein-RNA condensates with coexisting phases and complex material properties},
author = {Boeynaems, Steven and Holehouse, Alex S. and Weinhardt, Venera and Kovacs, Denes and Van Lindt, Joris and Larabell, Carolyn and Van Den Bosch, Ludo and Das, Rhiju and Tompa, Peter S. and Pappu, Rohit V. and Gitler, Aaron D.},
abstractNote = {Phase separation of multivalent protein and RNA molecules underlies the biogenesis of biomolecular condensates such as membraneless organelles. In vivo, these condensates encompass hundreds of distinct types of molecules that typically organize into multilayered structures supporting the differential partitioning of molecules into distinct regions with distinct material properties. The interplay between driven (active) versus spontaneous (passive) processes that are required for enabling the formation of condensates with coexisting layers of distinct material properties remains unclear. Here, we deploy systematic experiments and simulations based on coarse-grained models to show that the collective interactions among the simplest, biologically relevant proteins and archetypal RNA molecules are sufficient for driving the spontaneous emergence of multilayered condensates with distinct material properties. These studies yield a set of rules regarding homotypic and heterotypic interactions that are likely to be relevant for understanding the interplay between active and passive processes that control the formation of functional biomolecular condensates.},
doi = {10.1073/pnas.1821038116},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 16,
volume = 116,
place = {United States},
year = {2019},
month = {3}
}

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    Works referencing / citing this record:

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