Literature DB >> 35501484

Condensates in RNA repeat sequences are heterogeneously organized and exhibit reptation dynamics.

Hung T Nguyen1, Naoto Hori2, D Thirumalai3.   

Abstract

Although it is known that RNA undergoes liquid-liquid phase separation, the interplay between the molecular driving forces and the emergent features of the condensates, such as their morphologies and dynamic properties, is not well understood. We introduce a coarse-grained model to simulate phase separation of trinucleotide repeat RNAs, which are implicated in neurological disorders. After establishing that the simulations reproduce key experimental findings, we show that once recruited inside the liquid droplets, the monomers transition from hairpin-like structures to extended states. Interactions between the monomers in the condensates result in the formation of an intricate and dense intermolecular network, which severely restrains the fluctuations and mobilities of the RNAs inside large droplets. In the largest densely packed high-viscosity droplets, the mobility of RNA chains is best characterized by reptation, reminiscent of the dynamics in polymer melts. Our work provides a microscopic framework for understanding liquid-liquid phase separation in RNA, which is not easily discernible in current experiments.
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

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Year:  2022        PMID: 35501484     DOI: 10.1038/s41557-022-00934-z

Source DB:  PubMed          Journal:  Nat Chem        ISSN: 1755-4330            Impact factor:   24.274


  75 in total

1.  Germline P granules are liquid droplets that localize by controlled dissolution/condensation.

Authors:  Clifford P Brangwynne; Christian R Eckmann; David S Courson; Agata Rybarska; Carsten Hoege; Jöbin Gharakhani; Frank Jülicher; Anthony A Hyman
Journal:  Science       Date:  2009-05-21       Impact factor: 47.728

Review 2.  Liquid-liquid phase separation in biology.

Authors:  Anthony A Hyman; Christoph A Weber; Frank Jülicher
Journal:  Annu Rev Cell Dev Biol       Date:  2014       Impact factor: 13.827

Review 3.  Liquid phase condensation in cell physiology and disease.

Authors:  Yongdae Shin; Clifford P Brangwynne
Journal:  Science       Date:  2017-09-22       Impact factor: 47.728

4.  Physical principles of intracellular organization via active and passive phase transitions.

Authors:  Joel Berry; Clifford P Brangwynne; Mikko Haataja
Journal:  Rep Prog Phys       Date:  2018-01-09

5.  Physical Principles Underlying the Complex Biology of Intracellular Phase Transitions.

Authors:  Jeong-Mo Choi; Alex S Holehouse; Rohit V Pappu
Journal:  Annu Rev Biophys       Date:  2020-01-31       Impact factor: 12.981

Review 6.  Biomolecular Phase Separation: From Molecular Driving Forces to Macroscopic Properties.

Authors:  Gregory L Dignon; Robert B Best; Jeetain Mittal
Journal:  Annu Rev Phys Chem       Date:  2020-04-20       Impact factor: 12.703

Review 7.  Considerations and Challenges in Studying Liquid-Liquid Phase Separation and Biomolecular Condensates.

Authors:  Simon Alberti; Amy Gladfelter; Tanja Mittag
Journal:  Cell       Date:  2019-01-24       Impact factor: 41.582

Review 8.  Protein Phase Separation: A New Phase in Cell Biology.

Authors:  Steven Boeynaems; Simon Alberti; Nicolas L Fawzi; Tanja Mittag; Magdalini Polymenidou; Frederic Rousseau; Joost Schymkowitz; James Shorter; Benjamin Wolozin; Ludo Van Den Bosch; Peter Tompa; Monika Fuxreiter
Journal:  Trends Cell Biol       Date:  2018-03-27       Impact factor: 20.808

Review 9.  RNA Droplets.

Authors:  Kevin Rhine; Velinda Vidaurre; Sua Myong
Journal:  Annu Rev Biophys       Date:  2020-02-10       Impact factor: 12.981

Review 10.  Biomolecular condensates: organizers of cellular biochemistry.

Authors:  Salman F Banani; Hyun O Lee; Anthony A Hyman; Michael K Rosen
Journal:  Nat Rev Mol Cell Biol       Date:  2017-02-22       Impact factor: 94.444

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