Condensates in RNA repeat sequences are heterogeneously organized and exhibit reptation dynamics.
Journal
Nature chemistry
ISSN: 1755-4349
Titre abrégé: Nat Chem
Pays: England
ID NLM: 101499734
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
05
03
2021
accepted:
24
03
2022
pubmed:
3
5
2022
medline:
8
7
2022
entrez:
2
5
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35501484
doi: 10.1038/s41557-022-00934-z
pii: 10.1038/s41557-022-00934-z
doi:
Substances chimiques
RNA
63231-63-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
775-785Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
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