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FASEB J. 2019 Feb 11:fj201802715R. doi: 10.1096/fj.201802715R. [Epub ahead of print]

Functional interactions between scaffold proteins, noncoding RNAs, and genome loci induce liquid-liquid phase separation as organizing principle for 3-dimensional nuclear architecture: implications in cancer.

Author information

1
Lung Cancer Epigenetic, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
2
Laboratoire Croissance, Réparation, et Régénération Tissulaires (CRRET), Centre National de la Recherche Scientifique (CNRS) Équipe de Recherche Labellisée (ERL) 9215, Université Paris Est Créteil, Créteil, France.
3
Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, Kazan, Russian Federation.
4
Excellence Cluster Cardio Pulmonary System (ECCPS), Universities of Giessen-Marburg Lung Center (UGMLC), Giessen, Germany.
5
German Center of Lung Research (DZL), Giessen, Germany.

Abstract

The eukaryotic cell nucleus consists of functionally specialized subcompartments. These nuclear subcompartments are biomolecular aggregates built of proteins, transcripts, and specific genome loci. The structure and function of each nuclear subcompartment are defined by the composition and dynamic interaction between these 3 components. The spatio-temporal localization of biochemical reactions into membraneless nuclear subcompartments can be achieved through liquid-liquid phase separation. Based on this organizing principle, nuclear subcompartments are droplet-like structures that adopt spherical shapes, flow, and fuse like liquids or gels. In the present review, we bring into the spotlight seminal works elucidating the functional interactions between scaffold proteins, noncoding RNAs, and genomic loci, thereby inducing liquid-liquid phase separation as an organizing principle for 3-dimensional nuclear architecture. We also discuss the implications in different cancer types as well as the potential use of this knowledge to develop novel therapeutic strategies against cancer.-Rubio, K., Dobersch, S., Barreto, G. Functional interactions between scaffold proteins, noncoding RNAs, and genome loci induce liquid-liquid phase separation as organizing principle for 3-dimensional nuclear architecture: implications in cancer.

KEYWORDS:

biomolecular aggregates; chromosome territories; nuclear miRNAs; nuclear subcompartments; nucleolus

PMID:
30742773
DOI:
10.1096/fj.201802715R

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