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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

The eukaryotic cell nucleus consists of functionally specialized subcompartments. These nuclear sub‐compartments 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 sub‐compartments 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. FASEB J. 33, 5814–5822 (2019). www.fasebj.org